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 .
Claims 1-2, 4, 6-17, and 19-20, of record 4/2/2026, are pending and subject to prosecution. Claims 1, 4, 6-8, 11-12, 15-17, and 19-20 are amended. Claims 3, 5, and 18 are cancelled.
Status of Prior Rejections/Response to Arguments
RE: Objection to the drawings:
The submission of replacement drawings is effective to obviate the objection. The objection is withdrawn.
RE: Objection to the specification:
The amendments to the specification is effective to obviate the objection. The objection is withdrawn.
RE: Objection to claims 3-8:
The cancellation of claims 3 and 5 renders the objection thereto moot.
The amendment to claims 4 and 6-8 is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claims 2-5, 9-12, 15-17, and 20 under 35 U.S.C. 112(b):
The cancellation of claims 3 and 5 renders the rejection thereto moot.
The amendment to claims 4, 11-12, 15-17 and 20 is effective to obviate the rejection over those claims. The rejection over claims 4, 11-12, 15-17, and 20 is withdrawn.
The applicant asserts that the limitation “highly express” is a relative comparison to well-defined control populations rather than an absolute or subjective standard and that one of ordinary skill in the art would readily understand the limitation to refer to a measurable increase in expression relative to the specified control (Applicant Remarks, page 10).
This argument is not found persuasive. While the applicant argues that a comparison is made in relation to a defined control in each claim, “highly express” remains a term of degree. At issue is exactly what constitutes “high” expression. The applicant asserts that one of ordinary skill in the art would understand high expression to constitute any measurable increase in expression versus a control, but this is not consistent with the usage of the term within the art. One of ordinary skill be unlikely to consider any detectable increase (e.g., 0.1% or 0.01%) to signify high expression versus a control, but because the applicant has not defined the term, one of ordinary skill would unable to ascertain what precisely is denoted by “highly express”, even relative to a control.
The rejection over claims 9-12 is maintained.
RE: Rejection of claims 16-18 under 35 U.S.C. 101:
The cancellation of claim 18 renders the rejection thereto moot.
The amendment to claim 16 is effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claims 1-6, 13-14, 16, and 18 under 35 U.S.C. 103 over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1):
RE: Rejection of claims 1-8, 13-14, 16, and 18 under 35 U.S.C. 103 over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1), further in view of Haraszti et al. (Molecular Therapy, 2018):
The cancellation of claims 3, 5, and 18 renders the rejections thereto moot.
The amendment to claim 16 is effective to obviate the rejection over the claim.
The applicant asserts that the Kim et al. focus on the efficient production of exosomes rather than the effect of culture conditions on exosome activity or efficacy and that Makino et al. do not disclose parameters specifically for the controlled seeding of exosome-producing spheroids (Applicant Remarks, page 14-15). The applicant asserts that the invention requires a specific combination of parameters in order to achieve the claimed effects (Applicant Remarks, page 15-20). The applicant further asserts that the claimed method yields extracellular vesicles with unexpected and synergistic effects that could not have been predicted from the prior art (Applicant Remarks, page 20-22).
These arguments are not found persuasive. In response to applicant's argument that the references fail to show or suggest certain features of the invention, namely extracellular vesicles having improved properties, it is noted that the features upon which applicant relies are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Independent claim 1 requires only the production of extracellular vesicles in a method comprising particular steps and culture parameters. As long as the prior art combination renders obvious those steps and parameters, with an end product of extracellular vesicles, the limitations of the claim are met.
Regarding the assertion of unexpected results, in order for such an assertion to overcome a finding of obviousness, the scope of the claims and the experimental conditions used to achieve the results must be fully commensurate. See MPEP 716.02(d). The experimental results indicated in the specification were achieved by the method of Example 1.2, which discloses that 400 Wharton’s jelly-derived MSCs/well were seeded into microwells coated with 2-methacryloylexyethyl phosphorylcholine polymer with a depth and diameter of 500 µm and 200 µm, respectively. The figures cited by the applicant in the response to the previous Office action to support enhanced efficacy also use 400×200 wells with 400 cells, 500×600 wells with 400 cells, and 800×400 wells with 400 cells; however, the claimed method still encompasses a greater scope than these experimental conditions. Further, the disclosure of conditions that yield the alleged unexpected effects is insufficient to provide a basis for one of ordinary skill to extrapolate such effects to every combination of variables encompassed by the claims.
The rejections are maintained.
RE: Rejection of claims 1-6 and 13-20 under 35 U.S.C. 103 over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1), further in view of Lohan et al. (Frontiers in Immunology, 2017):
The cancellation of claims 3, 5, and 18 renders the rejection thereto moot.
The amendment to claim 16 is effective to obviate the rejection over claims 16-17.
The applicant asserts that Lohan et al. merely suggest autologous cells as a safer option to allogeneic MSCs and do not teach or suggest a solution to donor variation in extracellular vesicles (Applicant Remarks, page 23-24).
This argument is not found persuasive. A reference is prior art for all that it would have reasonably suggested to one of ordinary skill in the art. See MPEP 2123(I). One of ordinary skill would be able to readily recognize that the use of an single donor, e.g., an autologous donor as suggested by Lohan et al. to eliminate anti-donor responses, would intrinsically result in reduced donor variation in the stem cells, thus the extracellular vesicles they produce.
The rejection is maintained.
RE: Provisional rejection of claims 1-3, 5, 9-10, 16, and 18-20 on the ground of nonstatutory double patenting over claims 1-5 and 12 of co-pending Application No. 18289532:
RE: Provisional rejection of claims 1-4, 9-10, 16, and 18-20 on the ground of nonstatutory double patenting over claims 1-5, 10-11 of copending Application No. 18289530:
The cancellation of claims 3, 5, and 18 renders the rejections thereto moot.
The amendment to claim 16 is effective to obviate the rejection over the claim.
The applicant is reminded that 37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Non-statutory double patenting rejections may not be held in abeyance. See MPEP 714.02. The applicant did not traverse the NSDP rejections. The rejections are maintained.
New/Maintained Rejections
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.
Claims -9-12 and 16-17 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.
The term “highly express” in claims 9-12 and 16 is a relative term which renders the claims indefinite. The term “highly express” 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. It is unclear what level of expression would be required to meet this limitation. Dependent claim 17 is included in the rejection.
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.
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, 4-6, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1).
Regarding claims 1-2, 4-6, and 13-14: Kim et al. teach the production of exosomes (which read on “extracellular vesicles”) from three-dimensional MSC spheroids (See Abstract). MSCs are cultured as aggregates in hanging drops or in 96-well plates coated with poly-HEMA for 1, 3, and 5 days (See page 428, col. 2, full ¶2 and fig. 2). The exosomes are isolated by precipitation with a commercial kit (which reads on “chemical isolation”) for analysis, and spheroid cultured MSCs are determined to secrete more exosomes than MSCs in monolayers (See page 429, col. 1, full ¶2 and fig. 1). Thus, Kim teaches a method for producing extracellular vesicles derived from a three-dimensional spheroid-type cell aggregate comprising:(a) preparing the three-dimensional spheroid-type cell aggregate by 3 dimensionally (3D)-culturing stem cells in a microwell; and (b) isolating the extracellular vesicles from the three-dimensional spheroid-type cell aggregate, as required by claim 1. However, Kim et al. do not expressly teach cell spheroid culture in microwells with a diameter of 200-800 μm and depth of 100 to 1000 μm.
Makino et al. teach methods for producing undifferentiated cell spheroids from cells such as MSCs (See Abstract and ¶0015 and 0124). Culturing is performed on a sheet having a plurality of recesses (which reads on “microwell and “static culture”) (See ¶0015). The recesses (microwells) can have an opening that is 2000 µm or 1000 µm or less, such as 10-2000 µm, 10-1000 µm, 10-800 µm, or 10-500 µm, and the diameter of the recess bottom can be 10-2000 μm, 10 -1000 μm, 10-800 μm, 10-500 μm, 10-400 μm, or 10-300 μm (which read on “diameter of 200 to 800 µm “) (See ¶0094 and 0097). The depth of the recess (microwells) can be 10-1500 µm, 10-1000 µm, 10-800 µm, 10-500 µm, or 10-300 µm (which read on “depth of 100 to 1000 µm”) (See ¶0101). The cell culture sheet can be made of a non-cell adhesive substance or the walls of the recesses can be coated (which reads on “the microwell is coated”) with a non-adhesive material such as HEMA or MPC (See ¶0080-0086). The resulting cell spheroid has a diameter of 10-1500, 10-1000 µm, 10-800 μm, 10-600 μm, or 10-500 μm (which read on “average diameter of 65-133 μm”) (See ¶0015 and 0128). A spheroid can contain 10 cells, 100 cells, 1000 cells, 10000 cells, or more (which inherently reads on “dispersing and culturing… at a density of 200 to 600 cells/well”) (See ¶0129). Makino et al. teach that the cells can be cultured for 1-7 days (which reads on “3D culture… is performed for 1 to 10 days”) to achieve spheroid formation (See ¶0126).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Kim et al. to comprise spheroid formation in sheets comprising microwells as taught by Makino et al. One would be motivated to make this modification because Makino et al. teach that the use of the culture sheet comprising microwells enables easy and efficient production of cell spheroids that maintain their undifferentiated state (See ¶0016). Microwells with a diameter of 200-800 μm and depth of 100 to 1000 μm are likewise obvious in light of Kim et al. in view of Makino et al. because Makino et al. disclose methods of spheroid formation in microwells with overlapping ranges of diameter and depth. In the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. See MPEP 2144.05(I). There would be a reasonable expectation of success in doing so because the recessed sheet culture method of Makino et al. could be readily used to generate exosome-producing MSC spheroids in the method of Kim et al.
Claims 1-2, 4-8, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1), further in view of Haraszti et al. (Molecular Therapy, 2018), of record in IDS dated 5/4/2023.
The teachings of Kim et al. and Makino et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 7-8: Following the discussion of claims 1-2, 4-6, and 13-14, Kim et al., modified by Makino et al., render obvious a method of producing extracellular vesicles from microwell-formed cell spheroids but do not expressly teach filtration of the extracellular vesicles following centrifugation or isolation of the vesicles by tangential flow filtration.
Haraszti et al. teach methods for isolating exosomes (i.e., extracellular vesicles) produced from 3D culture of MSCs (See Abstract). In one protocol, culture supernatants are centrifuged at 300 × g and 10000 × g to remove debris, and the exosomes are passed through a 200 nm-pore filter prior to ultracentrifugation (which reads on “filtering the extracellular vesicles with a filter after centrifuging before the isolating of the extracellular vesicles”) (See fig. 2C). In another protocol, the exosomes are isolated from filtered supernatants subjected to ultrafiltration in a tangential flow filtration system (See fig. 2D).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Kim et al., modified by Makino et al., to comprise a filtration of the extracellular vesicles following centrifugation or isolation of the vesicles by tangential flow filtration, as taught by Haraszti et al. One would be motivated to make this modification because Haraszti et al. teach both protocols as enabling vesicle isolation from 3D MSC culture (See fig. 3). See MPEP 2143(I)(A) and (G). There would be a reasonable expectation of success in doing so because the vesicles produced by the method of Kim et al., modified by Makino et al., could be readily be subjected to either protocol taught by Haraszti et al.
Claims 1-2, 4-6, 13-14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1), further in view of Park et al. (The Anatomical Record, 2013) and Katsuda et al. (Proteomics, 2013).
The teachings of Kim et al. and Makino et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 16: Following the discussion of claims 1-2, 4-6, and 13-14, Kim et al., modified by Makino et al., render obvious a method of producing extracellular vesicles from microwell-formed cell spheroids but do not expressly teach the extracellular vesicles as highly expressing VEGFR2.
Park et al. teach that human adipose-derived stem cells (which read on “mesenchymal stem cells”) cultured in 3D aggregates stained for markers including KDR (which reads on “VEGF/R2”) whereas monolayer cultures did not (which reads on “highly express… as compared with… 2D-cultured mesenchymal stem cells”) (See Abstract).
Katsuda et al. teach that overexpression of molecules such as mRNAs and proteins in parent MSCs can be used to increase levels within extracellular vesicles (See page 1647, col. 1, ¶3).
One having ordinary skill in the art would therefore find it reasonable to infer that MSCs cultured in spheroids versus monolayer may have increased expression of VEGFR2, based on the teachings of Park et al. (See Abstract), and that extracellular vesicles produced from the spheroids would also exhibit higher VEGFR2 levels, as the teachings of Katsuda et al. suggest a correlation between expression levels in parent MSCs and extracellular vesicles (See page 1647, col. 1, ¶3). The extracellular vesicles generated by the method rendered obvious by Kim et al., modified by Makino et al., would therefore read on the claimed extracellular vesicles.
Claims 1-2, 4-6, 13-15, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1), further in view of Lohan et al. (Frontiers in Immunology, 2017).
The teachings of Kim et al. and Makino et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 15 and 19-20: Following the discussion of claims 1-2, 4-6, and 13-14, Kim et al., modified by Makino et al., render obvious a method of producing extracellular vesicles from microwell-formed cell spheroids but do not expressly teach a reduction in donor variation.
Lohan et al. teach that extracellular vesicles from allogeneic MSCs may contain immunogenic molecules that induce allo-immune responses (See page 6, col. 1, ¶1). Lohan et al. suggest that use of autologous MSCs for therapy may be the safer choice for avoiding unwanted immune responses (See Abstract).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Kim et al., modified by Makino et al., to comprise the use of autologous MSCs (which would read on “reduced in donor variation” and “reduced donor variation”). One would be motivated to make this modification because Lohan et al. suggest that the use of autologous MSCs could avoid potential unwanted immune responses caused by extracellular vesicles from allogeneic MSCs (See Abstract and page 6, col. 1, ¶1). There would be a reasonable expectation of success in doing so because the method of Kim et al., modified by Makino et al. could readily use autologous MSCs for generating extracellular vesicle-producing spheroids.
Claims 1-2, 4-6, 13-14, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Tissue Engineering and Regenerative Medicine, 2018) in view of Makino et al. (US 20220145241 A1), further in view of Park et al. (The Anatomical Record, 2013) and Katsuda et al. (Proteomics, 2013), further in view of Lohan et al. (Frontiers in Immunology, 2017).
The teachings of Kim et al., Makino et al., Park et al., Katsuda et al., and Lohan et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 17: Following the discussion of claims 1-2, 4-6, 13-14, and 16, Kim et al., modified by Makino et al., Park et al., and Katsuda et al., render obvious extracellular vesicles from microwell-formed cell spheroids that highly express VEGFR2 but do not teach reduced donor variation.
Lohan et al. teach that extracellular vesicles from allogeneic MSCs may contain immunogenic molecules that induce allo-immune responses (See page 6, col. 1, ¶1). Lohan et al. suggest that use of autologous MSCs for therapy may be the safer choice for avoiding unwanted immune responses (See Abstract).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Kim et al., modified by Makino et al., Park et al. and Katsuda et al., to comprise the use of autologous MSCs (which would read on “reduced in donor variation” and “reduced donor variation”). One would be motivated to make this modification because Lohan et al. suggest that the use of autologous MSCs could avoid potential unwanted immune responses caused by extracellular vesicles from allogeneic MSCs (See Abstract and page 6, col. 1, ¶1). There would be a reasonable expectation of success in doing so because the method of Kim et al., modified by Makino et al., Park et al., and Katsuda et al., could readily use autologous MSCs for generating extracellular vesicle-producing spheroids with reduced donor variation.
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 1-2, 9-10, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 12 of co-pending Application No. 18289532.
Regarding claims 1 and 19-20: Co-pending claim 1 recites a method for preventing or treating neurological diseases and damage comprising; (a) preparing a three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm; and (b) preparing extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate by isolating extracellular vesicles from the three-dimensional spheroid-type cell aggregate; and (c) treating the extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate prepared in step (b) to a subject in need thereof. Co-pending claim 3 recites the method of co-pending claim 1, wherein the 3D culture in step (a) is static culture. Co-pending claim 4 recites the method of co-pending claim 1, wherein the 3D culture in step (a) is performed by dispersing and culturing the mesenchymal stem cells in a microwell at a density of 200 to 600 cells/well. Co-pending claim 12 recites a method for producing a composition for promoting neurogenesis comprising extracellular vesicles derived from three-dimensional spheroid-type cell aggregate, comprising: (a) preparing three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm; and (b) isolating extracellular vesicles from the three-dimensional spheroid-type cell aggregate. Because the preamble of the co-pending and instant claims do not limit the structure of the inventions, the combined limitations of the co-pending claims render obvious the instant claims. See MPEP 2111.02(I).
Regarding claim 2: Following the discussion of claims 1 and 18-20, co-pending claim 2 recites the method of claim 1, wherein the stem cells are at least one selected from the group consisting of mesenchymal stem cells, pluripotent stem cells, induced pluripotent stem cells and embryonic stem cells. The co-pending claim anticipates the instant claim.
Regarding claims 9-10: Following the discussion of claims 1 and 18-20, co-pending claim 5 recites the method of co-pending claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of miR-27a, miR-132, miR-146a, and miR-146b as compared with extracellular vesicles derived from spheroidal cell aggregates obtained by 3D dynamic culture of mesenchymal stem cells and extracellular vesicles derived from mesenchymal stem cells obtained by 2D culture. The co-pending claims render obvious the instant claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 9-10, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 10-11 of co-pending Application No. 18289530.
Regarding claims 1 and 19-20: Co-pending claim 1 recites a method for promoting angiogenesis comprising: (a) preparing a three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm; (b) preparing extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate by isolating extracellular vesicles from the three-dimensional spheroid-type cell aggregate; and (c) treating the extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate prepared in step (b) to a subject in need thereof. Co-pending claim 3 recites the method for promoting angiogenesis of co-pending claim 1, wherein the 3D culture in step (a) is static culture. Co-pending claim 4 recites the method for promoting angiogenesis of co-pending claim 1, wherein the 3D culture in step (a) is performed by dispersing and culturing the mesenchymal stem cells in a microwell at a density of 200 to 600 cells/well. Co-pending claim 10 recites an in vitro method for promoting angiogenesis comprising: (a) preparing a three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm; (b) preparing extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate by isolating extracellular vesicles from the three-dimensional spheroid-type cell aggregate; and (c) treating the extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate prepared in step (b) to in vitro cells. Co-pending claim 11 recites a method for producing a composition for promoting angiogenesis comprising extracellular vesicles derived from a three-dimensional spheroid-type cell aggregate, comprising: (a) preparing a three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm; and (b) isolating extracellular vesicles from the three-dimensional spheroid-type cell aggregate. The preamble of the co-pending claims do not structurally limit the inventions and therefore lacks patentable weight. See MPEP 2111.02(I). The combined limitations of the co-pending claims render obvious the instant claims.
Regarding claim 2: Following the discussion of claims 1 and 19-20, co-pending claim 2 recites the pharmaceutical method for promoting angiogenesis of co-pending claim 1, wherein the stem cells are at least one selected from the group consisting of mesenchymal stem cells, pluripotent stem cells, induced pluripotent stem cells and embryonic stem cells. The co-pending claims render obvious the instant claim.
Regarding claims 9-10: Following the discussion of claims 1 and 19-20, co-pending claim 5 recites the method for promoting angiogenesis of co-pending claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of miR-27a, miR-132, miR-146a, miR-146b, miR-184, and miR-210 as compared with extracellular vesicles derived from a spheroid-type cell aggregate obtained by 3D dynamic culture of mesenchymal stem cells and extracellular vesicles derived from mesenchymal stem cells obtained by 2D culture. The co-pending claims render obvious the instant claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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, Christopher M Babic, can be reached at 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.
/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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