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 the Claims
Claims 1-12 and 18-24 are pending (claim set as filed on 06/16/2023).
Election/Restrictions
Applicant’s election without traverse of Group I, process of making claims, in the reply filed on 02/13/2026 is acknowledged.
Claims 12 and 18-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Therefore, only claims 1-11 are under examination.
Priority
This application is a 371 of PCT/KR2021/018761 filed on 12/10/2021, which claims a foreign application to KR 10-2020-0174891 filed on 12/14/2020.
Examiner’s note: Receipt of the Certified Copy of Foreign Priority Application has been received on 06/14/2023. However, the foreign priority date is the effective filing date of the claimed invention if: (a) the foreign application supports the claimed invention under 112(a); and (b) the Applicant has perfected the right of priority by providing: (i) a certified copy of the priority application, (ii) a translation of the priority application (if not in English), and (iii) there is a statement that the U.S. application is an accurate translation of the foreign priority document, so all subject matter in the U.S. application is supported in the foreign priority document.
Accordingly, the effective filing date of the claimed invention is the PCT filing date of 12/10/2021 until the foreign priority requirement(s) is/are perfected (see MPEP 215-216).
Drawings
The drawings filed on 06/14/2023 have been accepted.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 06/14/2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
Claim Rejections - 35 USC §112, Indefinite
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.
Claim 3 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.
Regarding claim 3, the parenthetical phrase of “(Wharton’s jelly-derived MSCs, WJ-MSCs)” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention (MPEP 2173.05(d): Exemplary Claim Language).
Claim Rejections - 35 USC §103, Obviousness
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
Claims 1, 4, and 6-11 are rejected under 35 U.S.C. 103 as being unpatentable over 1°Kim (US Patent no. 12,280,148 B2, with a PCT filing date of 06/03/2021) in view of 2°Kim (US Patent no. 11,248,024 B2, with a pre-grant publication date of 07/30/2020).
Examiner’s note: Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate (see MPEP 215 and 216).
1°Kim’s general disclosure relates to the field of extracellular vesicles production (see col. 1: Background art) and the use of a peptide for promoting extracellular vesicle production efficiently and uniformly mass-produce extracellular vesicles (see abstract & col. 6, lines 43-49).
Kim teaches “a composition for promoting extracellular vesicle production containing a peptide derived from Noxa protein and to a method for producing extracellular vesicles (EV) by using the same and, specifically, to a composition containing a peptide derived from Noxa protein that plays a key role in apoptosis and to a method for efficiently mass-producing extracellular vesicles by using a solution containing a sugar” (see abstract & col. 1, lines 14-21, & col. 2, lines 39-60). In particular, Kim teaches “a method for producing extracellular vesicles, the method including the following steps: a medium preparing step of preparing a medium containing: at least one peptide selected from the group consisting of peptides containing amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 21; and a solution containing a sugar; and a mixing step of mixing the medium and a cell line. In the present invention, the cell line may be one selected from the group consisting of mouse colon carcinoma (CT26), human cervical cancer (HeLa), human renal epithelium (HEK293), mouse adipocytes (3T3-Ll), and human mesenchymal stem cells (HMSC), and may be for example HeLa or HEK293, but is not limited thereto” (see col. 5, lines 36-50, & Examples 1-2: Culture & EV Production). Kim teaches solutions/compositions containing glucose, MOPS, NaCl, KCl, Na/K-gluconate, sucrose, NaPO4, and KPO4 (see Example 2 or Tables 2-3).
Regarding claim 4 pertaining to the trypsin, Kim teaches “cancer cell lines were cultured prior to testing the activity to induce extracellular vesicle production by the Noxa protein-derived peptide and the derivatives thereof in preparative Example 1. Dulbecco’s modified eagle medium (DMEM), RPMI 1640, fatal bovine serum (FBS), trypsin-ethylenediaminetetraacetic acid (trypsin-EDTA), and Hank’s balanced salt solution (HBSS) required for culture” (see col. 9, lines 40-48: Experimental Example 1).
Regarding claim 6 pertaining to the duration, Kim teaches the experimental group was treated with the peptide and after 10 minutes, the generation of extracellular vesicles was observed (see col. 9-10: Experimental Example 2).
Regarding claims 8-9 pertaining to the sugar, Kim teaches the sugar may be at least one selected from the group consisting of glucose, sorbitol, and sucrose (see col. 3, lines 64-66); the concentration of glucose may be 5-50 mM (see col. 4, lines 1-18, & col. 5, lines 28-35); the concentration of sucrose may be 100-250 mM (see col. 4, lines 19-26).
Regarding claim 10 pertaining to 3-(N-morpholino)propanesulfonic acid (MOPS), Kim teaches the concentration of MOPS contained in the solution may be 7 to 13 mM (see col. 4, lines 40-45, & col. 5, lines 28-35).
Regarding claim 11 pertaining to the isolation, Kim teaches after culturing to produce the extracellular vesicles, the vesicles were centrifuged and quantified (see experimental example 6).
However, 1°Kim does not teach: a peptide composed of the amino acid sequence of SEQ ID NO: 1 (claim 1’s limitation); or is contained at a concentration of 0.1-5.0 µM in the medium composition (claim 7).
2°Kim teaches a peptide is derived from Noxa protein and comprises 16 amino acid residues including MTD (see abstract). Kim further teaches amino acids sequences of the peptide are given in Table 2 where SEQ ID NO: 1 (Sequencing List: KLNFRQKLLNLISKLFCSGT) and SEQ ID NO: 4 (MPGKKARKNAQPSPARAPAELEVECATQLRRFGD-KLNFRQKLLNLISKLFCSGT) (see col. 9, Example 1 and Table 2). Claim interpretation: SEQ ID NO: 1 and 4 of the prior art reads on the instant SEQ ID NO: 1 of the claimed invention.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ or substitute the Noxa peptide of SEQ ID NO: 1 or 4 such as taught by 2°Kim in the method of 1°Kim for extracellular vesicle production. The ordinary artisan would have been motivated to do so and would have also had a reasonable expectation of success is because both amino acid sequences of the prior arts are Noxa protein/peptides and thus, it would be deemed a simple substitution of one known element or an obvious variant for another to obtain predictable results (MPEP 2141(III)(B)).
Furthermore, regarding the concentration of the peptide, the MPEP 2144.05(II)(A) states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where 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”. For instance, 1°Kim discloses that “the concentration of the peptide contained in the solution may be 10 to 80 µM … but is noted limited thereto” (see col. 3, lines 58-63). 1°Kim further teaches experimentation with various peptide concentrations (see, e.g., col. 13, lines 1-4, & experimental examples). Based upon the overall objective provided by 1°Kim with respect maximizing efficiency of the use of a peptide for promoting extracellular vesicle production efficiently and uniformly mass-produce extracellular vesicles (see 1°Kim at abstract & col. 6, lines 43-49), the adjustments of particular conventional working condition (e.g., concentration of the peptide) is deemed a matter of judicious selection and routine optimization which is within the purview of the skill artisan. Therefore, the disclosure of 1°Kim establishes the conditions of variable parameters such that one of ordinary skill in the art would recognize that the peptide concentration is a result effective variable dependent upon the cell type used and/or additional components in the culture medium. This is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Absent any teaching of criticality by the Applicant concerning the peptide concentration, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variable which can be met as a matter of routine optimization (MPEP 2144.05 II).
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over 1°Kim in view of 2°Kim as applied to claims 1, 4, and 6-11 above, and in further view of Ding (US 2020/0297761 A1 - previously cited).
The combined disclosures of 1°Kim and 2°Kim, herein simply referred to as modified-Kim, is discussed above as it pertains to a method for producing extracellular vesicles comprising culturing mesenchymal stem cells in a medium containing SEQ ID NO: 1, glucose, sucrose, and MOPS.
However, modified-Kim does not teach: MSCs derived from at least one selected from the group consisting of a bone marrow, an embryo, an umbilical cord, a muscle, a fat, and a nerve tissue (claim 2); or derived from an umbilical cord (Wharton’s jelly-derived MSCs, WJ-MSCs (claim 3).
Ding’s general disclosure relates to a pharmaceutical composition comprising exosomes (i.e., extracellular vesicles) of mesenchymal stem cells (see abstract & ¶ [0001], [0027]). Ding discloses “mesenchymal stem cells (MSCs) include various types derived from different sources, e.g., bone marrow mesenchymal stem cells (BM-MSCs), umbilical cord blood mesenchymal stem cells (UCB-MSCs), human umbilical cord mesenchymal stem cells (HUCMSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) … the exosomes are derived from the mesenchymal stem cell which is cultured” (see ¶ [0013], [0025]). Ding further teaches Wharton’s jelly (WJ) was isolated from blood vessels and amnion in 24 hours (see ¶ [0043]-[0044]).
It would have been obvious to one of ordinary skill in the art to employ or substitute mesenchymal stem cells derived from BM-MSCs, UCB-MSCs, MDSCs, ADSCs, or WJ-MSCs such as taught by Ding in the method of modified-Kim for the production of extracellular vesicles. The ordinary artisan would have been motivated to do so is because Ding discloses that MSCs are known to be obtained from various different sources and thus, it would be deemed a simple substitution of one known element for another to obtain predictable results (MPEP 2141(III)(B)). The ordinary artisan would have had a reasonable expectation of success is because the references are directed to exosome production from MSCs.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over 1°Kim in view of 2°Kim as applied to claims 1, 4, and 6-11 above, and in further view of Cho (US 2023/0220348 A1, with a PCT filing date of 04/28/2021).
The combined disclosures of 1°Kim and 2°Kim, herein simply referred to as modified-Kim, is discussed above as it pertains to a method for producing extracellular vesicles comprising culturing mesenchymal stem cells in a medium containing SEQ ID NO: 1, glucose, sucrose, and MOPS.
However, modified-Kim does not teach: wherein the second culturing step is performed in an orbital shaking culture manner (claim 5).
Cho’s general disclosure relates to “a method for producing extracellular vesicles from three-dimensionally cultured stem cells. The method of the present disclosure can produce stem cell-derived extracellular vesicles with a high yield through orbital shaking culture of stem cell aggregates in the presence of TGF-β and thus can be usefully used in an industrial-scale mass production process of exosomes” (see abstract & ¶ [0029]-[0030]).
It would have been obvious to one of ordinary skill in the art to perform the culturing step in an orbital shaking manner such as taught by Cho in the method of modified-Kim because Cho teaches high yield production of extracellular vesicles through orbital shaking culture which can be usefully used in an industrial-scale mass production process of exosomes which is the objective of the primary reference of 1°Kim. The ordinary artisan would have had a reasonable expectation of success is because the cited prior arts are directed to the production of extracellular vesicles from stem cells.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent no. 12,280,148 B2 in view of Ding (US 2020/0297761 A1 - previously cited) and 2°Kim (US Patent no. 11,248,024 B2). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Patent ‘148 teaches “a medium for extracellular vesicle production, the medium comprising: at least one peptide selected from the group consisting of SEQ ID NOs: 2 and 5-15; and a solution containing a sugar”; “wherein the sugar is at least one selected from the group consisting of glucose, sucrose, and sorbitol”; and “wherein the solution further contains 3-(N-morpholino) propanesulfonic acid (MOPS)” (see claims 1-4 of Patent ‘148).
However, Patent ‘148 does not teach: culturing mesenchymal stem cells in a medium comprising a peptide composed of the amino acid sequence of SEQ ID NO: 1 (claim 1’s limitations); or wherein the MSCs are derived from bone marrow, umbilical cord, muscle, fat, or Wharton’s jelly (claims 2-3).
Regarding the mesenchymal stem cells, Ding’s general disclosure relates to a pharmaceutical composition comprising exosomes (i.e., extracellular vesicles) of mesenchymal stem cells (see abstract & ¶ [0001], [0027]). Ding discloses “mesenchymal stem cells (MSCs) include various types derived from different sources, e.g., bone marrow mesenchymal stem cells (BM-MSCs), umbilical cord blood mesenchymal stem cells (UCB-MSCs), human umbilical cord mesenchymal stem cells (HUCMSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) … the exosomes are derived from the mesenchymal stem cell which is cultured” (see ¶ [0013], [0025]). Ding further teaches Wharton’s jelly (WJ) was isolated from blood vessels and amnion in 24 hours (see ¶ [0043]-[0044]). Therefore, it would have been obvious to one of ordinary skill in the art to employ mesenchymal stem cells derived from BM-MSCs, UCB-MSCs, MDSCs, ADSCs, or WJ-MSCs such as taught by Ding in Patent ‘148’s medium for the production of extracellular vesicles. The ordinary artisan would have been motivated to do so is because Ding discloses that MSCs are known to be obtained from various different sources used for culturing to produce exosomes and thus, it would be deemed a simple combination of one known element to obtain predictable results (MPEP 2141(III)(B)). The ordinary artisan would have had a reasonable expectation of success is because both are directed to exosome production.
Regarding the peptide, 2°Kim teaches a peptide is derived from Noxa protein and comprises 16 amino acid residues including MTD (see abstract). Kim further teaches amino acids sequences of the peptide are given in Table 2 where SEQ ID NO: 1 (Sequencing List: KLNFRQKLLNLISKLFCSGT) and SEQ ID NO: 4 (MPGKKARKNAQPSPARAPAELEVE-CATQLRRFGD-KLNFRQKLLNLISKLFCSGT) (see col. 9, Example 1 and Table 2). Claim interpretation: SEQ ID NO: 1 and 4 of the prior art reads on the instant SEQ ID NO: 1 of the claimed invention. Therefore, it would have been obvious to one of ordinary skill in the art to employ or substitute the Noxa peptide of SEQ ID NO: 1 or 4 such as taught by 2°Kim in Patent ‘148’s medium for extracellular vesicle production. The ordinary artisan would have been motivated to do so and would have also had a reasonable expectation of success is because both amino acid sequences of the instant invention and 2°Kim are Noxa protein/peptides and thus, it would be deemed a simple substitution of one known element for another to obtain predictable results (MPEP 2141(III)(B)).
Conclusion
No claims were allowed.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653