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 .
Priority
The instant application, filed 13th of November 2024 claims priority as a continuation of U.S. Application Number 17/601,775, filed 06 October 2021, which claims priority from the 371 application of PCT/KR2020/006574 filed on 20th of May 2020.
Claim Status
Applicant filed claims 1-13 on Nov. 13, 2024. In a preliminary amendment, Applicant has canceled claims 1-13 and added new claims 14-19 on the 13th of November 2024.
Currently, claims 14-19 are pending in this application and are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 13th of Nov. 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Applicant is reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability. Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
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 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kim, Soo, et al. (International journal of molecular sciences 19.10: 3119, published Oct. 2018, hereinafter as “Kim”) and Domenis, Rossana, et al. (Scientific reports 8.1: 13325, published 2018, hereinafter as “Domenis”).
Regarding claim 14, Kim discloses a method for producing stem cell-derived exosomes, the method comprising: wherein the stem cell is an induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) (see e.g. abstract and methods sec.).
Kim does not explicitly disclose culturing stem cells in a cell culture medium containing interferon-γ.
However, the prior art of Domenis suggests that mesenchymal stem cells (MSC)-derived exosomes treated with (interferon-γ, IFN- γ), could modulate the expression of pro-inflammatory genes, thus reducing or delaying inflammation and enhance wound healing (see e.g. discussion section, fig. 1-4, pages 1-3, 8-9).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the method for producing stem cell-derived exosomes, as taught by Kim, to incorporate a cell culture medium with IFN- γ, as taught by Domenis, with a reasonable expectation of success because one of ordinary skill in the art would know that wound healing increased following exosome treatment, and the increase in expression was more significant following treatment with iMSC-exosomes (as taught by Kim, see e.g. page 8). Further, a person of ordinary skill in the art would know that mesenchymal stem cells (MSC)-derived exosomes treated with (interferon-γ, IFN- γ), could modulate the expression of pro-inflammatory genes, thus reducing or delaying inflammation and enhance wound healing (as taught by Domenis, see e.g. discussion section, fig. 1-4, pages 1-3, 8-9). Further, both Kim and Domenis disclose methods for obtaining MSC-derived exosomes for promoting wound healing (see e.g. abstracts, respectively). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success.
Regarding claim 15, Kim discloses washing the cultured stem cells, followed by additional culturing in a cell culture medium; and isolating exosomes (see e.g. pages 10-12).
Regarding claim 16, Kim discloses wherein the cell culture medium contains fetal bovine serum free of exosomes (see e.g. pages 10-12).
Regarding claim 17, as stated supra, Kim discloses a method of culturing stem cells in a cell culture medium, wherein the stem cell is an induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC).
While Kim and Domenis do not explicitly describe increasing stemness of stem cells, they do carry out the same claimed method steps as Applicant and therefore are deemed to include the same effect baring evidence to the contrary.
MPEP at 2113 states “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process”. Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims."
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the method for producing stem cell-derived exosomes, as taught by Kim, and incorporate a cell culture medium with IFN- γ, as taught by Domenis, which would have naturally caused an increase in stemness of the stem cells with a reasonable expectation of success. Additionally, a person of ordinary skill in the art would know that the expression of genes involved in wound healing increased following exosome treatment, and the increase in expression was more significant following treatment with iMSC-exo than with MSC-exo (as taught by Kim, see e.g. page 8). Further, both Kim and Domenis disclose methods for obtaining MSC-derived exosomes for promoting wound healing (see e.g. abstracts, respectively). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success.
Kim does not explicitly disclose culturing stem cells in a cell culture medium containing interferon-γ.
However, the prior art of Domenis suggests that mesenchymal stem cells (MSC)-derived exosomes treated with (interferon-γ, IFN- γ), could modulate the expression of pro-inflammatory genes, thus reducing or delaying inflammation and enhance wound healing (see e.g. discussion section, fig. 1-4, pages 1-3, 8-9).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the method for producing stem cell-derived exosomes, as taught by Kim, to incorporate a cell culture medium with IFN- γ, as taught by Domenis, with a reasonable expectation of success because one of ordinary skill in the art would know that mesenchymal stem cells (MSC)-derived exosomes treated with (interferon-γ, IFN- γ), could modulate the expression of pro-inflammatory genes, thus reducing or delaying inflammation and enhance wound healing (as taught by Domenis, see e.g. discussion section, fig. 1-4, pages 1-3, 8-9). Further, both Kim and Domenis disclose methods for obtaining MSC-derived exosomes for promoting wound healing (see e.g. abstracts, respectively). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success.
Regarding claim 18, Kim discloses wherein the induced pluripotent stem cell of human tissue origin (see e.g. abstract, pages 10-12).
Regarding claim 19, Kim discloses wherein the human or animal tissue is selected from the group consisting of umbilical cord (i.e. human Wharton’s jelly)(see e.g. abstract, pages 10-12).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over Varkouhi, et al. (Anesthesiology 130.5, published May 2019, hereinafter as "Varkouhi," cited IDS 11/13/2024), Sabapathy, Vikram, and Sanjay Kumar ((Journal of cellular and molecular medicine 20.8: 1571-1588, published 2016, hereinafter as “Sabapathy”), Zhao C, Ikeya M. (Stem Cells Int.; 9601623, published 2018, hereinafter as “Zhao”), and Phinney, et al. (Nature communications 6.1: 8472, published 2015; hereinafter as "Phinney," cited IDS 11/13/2024).
Regarding claim 14 and 17, Varkouhi discloses a method for producing stem cell-derived exosomes (i.e. extracellular vesicles)(see e.g. page 784), the method comprising: culturing stem cells in a cell culture medium containing interferon-γ (see e.g. abstract, page 778-784).
Varkouhi is silent regarding wherein the stem cell is an induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) and a method for increasing stemness of stem cells.
However, the prior art of Sabapathy discloses that iPSC-derived MSCs (iMSCs) are an attractive source of MSCs because during reprogramming process, the cells undergo rejuvination, exhibiting better cellular vitality such as survival, proliferation, and differentiations potentials (see e.g. abstract, fig. 1, table 2 and 4). Further, Sabapathy discloses that the iMSCs are reported to be superior when compared to the adult MSCs regarding cell proliferation, immunomodulation, cytokines profiles, microenvironment modulating exosomes and bioactive paracrine factors secretion as well as being an alternate source of therapeutically active MSCs in different cell types such as lung and airway epithelial cells (see e.g. abstract, fig. 1, table 2 and 4). Additionally, the prior art of Zhao discloses that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) are known to secrete exosomes for therapeutic purposes (see e.g. abstract, page 4-5).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the methods for producing stem cell-derived exosomes, as taught of Varkouhi, to incorporate wherein the stem cell is an induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC), as taught by Sabapathy and Zhao, with a reasonable expectation of success because one of ordinary skill in the art would know that iMSCs exhibiting better cellular vitality such as survival, proliferation, and differentiations potentials (as taught by Sabapathy, see e.g. abstract, fig. 1, table 2 and 4).
As stated supra, Varkouhi et al does not explicitly describe increasing stemness of stem cells, but they do carry out the same claimed method steps as Applicant and therefore are deemed to include the same effect baring evidence to the contrary.
MPEP at 2113 states “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process”. Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims."
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the method for producing stem cell-derived exosomes with a cell culture medium having IFN- γ, as taught by Varkouhi et al., with a reasonable expectation of success because one of ordinary skill in the art would know that exosomes from MSC would naturally have greater self-renewal capacity (i.e. stemness, see Spec. para. 134) which reads on the claimed limitation of increase in stemness of the stem cells (as taught by Varkouhi et al., see e.g. page 786)
Regarding claim 15, Varkouhi discloses methods for isolating exosomes (see e.g. page 779).
Varkouhi does not explicitly state the steps of washing the cultured stem cells followed by additional culturing.
However, Varkouhi cites the prior art of Phinney et al. (2015) for teaching the isolation of Mesenchymal stromal cell-derived extracellular vesicles (page 779, see extracellular vesicle isolation).
Regarding claim 11, Phinney teaches conditioned medium from MSCs was collected every 24 hours and was subjected to successive centrifugation to remove cells and cell debris (page 13, see Isolation of MVs). Further, Phinney teaches that vesicles isolated from conditioned medium from human MSCs were pooled (page 13; see col. 2, para. 1 ). Claim Interpretation: Broadest Reasonable Interpretation - collecting the condition media every 24 hours followed by pooling the condition media as taught by Phinney reads on the claimed washing the culture of stem cells followed by additional culturing in a cell culture media.
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the methods of Varkouhi with a washing step as taught by Phinney with a reasonable expectation of success. A person of ordinary skill in the art would have been motivated to include the washing step with a reasonable expectation of success because Phinney teaches the beneficial removal of cell and cell debris when isolating exosomes and Varkouhi is also drawn to the production and isolation of exosomes (see e.g. page 13).
Regarding claim 16, Varkouhi discloses wherein the cell culture medium contains fetal bovine serum free of exosomes (see e.g. page 779).
Regarding claim 18-19, Varkouhi discloses wherein the induced pluripotent stem cell of human tissue origin from umbilical cord (see e.g. page 779 and 784).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
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 14-19 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 10-17 of copending Application Number 17/601,775 (the ‘775 application), in view of Guo-Wen Hu et al. (Stem Cell Res Ther. 2015; 6: 10, published 2015).
The instant claims are directed to A method for producing stem cell-derived exosomes, and increasing stemness of stem cells the method comprising: culturing stem cells in a cell culture medium containing interferon-γ, wherein the stem cell is an induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC)(see claims 14 and 17).
The co-pending ‘775 application’s claims are directed to a method for producing stem cell-derived exosomes and increasing stemness of stem cells, the method comprising a step of: culturing stem cells in a cell culture medium containing at least one selected from the group consisting of interferon-γ (see claims 10 and 13).
Both claims are direct to producing stem cell-derived exosomes with interferon-γ.
The co-pending claims do not recite an induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC).
However, an induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) would have been obvious in view of the prior art in view of Guo-Wen Hu et al..
One would have used the c-opending methods in view of the teachings of the cited prior art for the benefits of iPSC-derived mesenchymal stem cells (iMSCs) possess powerful proliferation, differentiation, and therapeutic effect, as taught in the prior art (see e.g. abstract). One would have been motivated to do so with a reasonable expectation of success because the cited prior art teaches that iPSC-derived mesenchymal stem cells (iMSCs) possess powerful proliferation, differentiation, and therapeutic effects. The cited prior art also teaches that implanted iMSCs-Exo was able to protect limbs from ischemic injury via the promotion of angiogenesis, which indicated that iMSCs-Exo may be a novel therapeutic approach in the treatment of ischemic diseases (See e.g. abstract). Therefore, it would have been obvious to use the co-pending methods and induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) as taught by Guo-Wen Hu et al.. Therefore, the instant claims would have been obvious in view of the co-pending claims and the cited prior art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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