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 1-12, of record 6/24/2024, are pending and subject to prosecution.
Priority
The instant application is a national stage entry of PCT/KR2022/021212 (filed 12/23/2022). Acknowledgement is made of the applicant’s claim for foreign priority to Republic of Korea application 10-2021-0187681 (filed 12/24/2021).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in ¶0108 of the instant application’s PG Pub. The applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP 608.01.
The use of the terms Opadry, TrypLE Express, Alexa Fluor, and TruSeq, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1-4, 6, and 8 are objected to because of the following informalities:
In line 4 of claim 1, “obtained“ should be deleted.
In line 2 of claim 2 and line 5 of claim 3, “step” should be deleted. Additionally, “a” should be inserted after “treating” in line 2.
Claims 4 and 8 should be rewritten to recite “one or more genes selected from the group consisting of GAS1, OSR2, DMKN, and SBSN” to form a proper Markush grouping.
In line 3 of claim 6, “cell isolation” should be replaced with “stem cell recovery” to improve consistency.
Appropriate correction is required.
Claim Interpretation
Claim 6 recites the limitation “wherein the skin-derived stem cells maintain a cell shape and a cell size until ninth subculture after tissue culture and cell isolation”. This limitation is interpreted as requiring the cells to maintain any starting cell shape and size through nine subcultures.
Claims 7-12 recite the limitation “skin-derived stem cells prepared by the method according to claim 1”. The cells are defined using product-by-process language. Product-by-process limitations are considered only in so far as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product as claimed is the same or obvious over a product of the prior art (i.e., is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113. In the instant application, because the method of claim 1 does not distinguish the cells from cells generated by other methods, the limitation is interpreted as encompassing any skin-derived stem cells.
Claims 10-12 also recite a pharmaceutical, quasi-drug, or cosmetic composition comprising skin-derived stem cells prepared by the method according to claim 1 as an active ingredient. Because the claims recite no other ingredients and require only skin-derived stem cells as an active ingredient, the broadest reasonable interpretation of the compositions is considered to encompass skin-derived stem cells on their own, and the adjectives “pharmaceutical”, “quasi-drug”, and “cosmetic” are not considered to be further limiting.
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 4 and 8 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 “increased” in claims 4 and 8 is a relative term which renders the claims indefinite. The term “increased” is not defined by the claim, 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 to what the expression of GAS1, OSR2, DMKN, or SBSN must be “increased” relatively, therefore, one would be unable to determine infringement upon the claimed invention.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 7 and 9-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation.
Regarding claims 7 and 9-12: Claims 7 and 9 are directed to skin-derived stem cells prepared by the method according to claim 1. Claims 10-12 are directed to a pharmaceutical, quasi-drug, or cosmetic composition comprising skin-derived stem cells prepared by the method according to claim 1 as an active ingredient. The broadest reasonable interpretation of the cells and compositions is considered to cover any skin-derived stem cells. Based upon this interpretation, the claims are analyzed as follows:
Step 1: The claims are directed to compositions comprising skin-derived stem cells, which are a statutory category of matter (Step 1: YES).
Step 2A, prong 1: Skin-derived stem cells are nature-based products. When a claimed composition includes a nature-based product, further analysis is taken to determine if the claimed composition recites a nature-based product judicial exception by comparing the claimed composition to the closest naturally occurring counterpart to determine if the claimed composition has markedly different characteristics than the counterpart.
The closest naturally occurring counterpart of a skin-derived stem cell is a naturally occurring skin-derived stem cell. Skin-derived mesenchymal cells express CD29, CD44, CD73, CD90, and CD105 but not CD14, CD34, and CD45 (See Orciani et al., page 127, col. 1, full ¶2 and col. 2, ¶1; Al-Nbaheen et al., page 36, col. 1, ¶2). The claimed cells read on naturally occurring cells and are therefore considered to read on a product of nature judicial exception (Step 2, prong 1: YES).
Step 2A, prong 2: The claims are directed to a product and do not recite any structure that serves to integrate the composition into a practical application (Step 2, prong 2: NO).
Step 2B: There are no additional elements required by the claims.
Claims 7 and 9-12 do not qualify as eligible subject matter and are rejected under 35 U.S.C. 101.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 7 and 9-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Orciani et al. (Skin Pharmacology and Physiology, 2010), evidenced by Al-Nbaheen et al. (Stem Cell Reviews and Reports, 2013).
Regarding claims 7 and 9-12: Orciani et al. teach morphological and functional features of mesenchymal stem cells from skin (See Abstract). The isolated cells expressed CD29, CD44, CD73, CD90, and CD105 but not CD14 or CD34 (See page 127, col. 1, full ¶2 and col. 2, ¶1). Orciani et al. teach that skin-derived mesenchymal cells could be a promising source of cells for skin transplantation (which reads on “skin regeneration or wound treatment” and “active ingredient”) (See page 131, col. 2, full ¶2).
While Orciani et al. do not expressly teach whether the cells express CD45, Al-Nbaheen et al. teach that CD14, CD34, and CD45 are absent from the surface of skin-derived mesenchymal stem cells (See page 36, col. 1, ¶2). The cells taught by Orciani et al. therefore anticipate the claimed cells and compositions.
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.
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, 5-7, and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (WO 2020067774 A1, machine translation), in view of Thangapazham et al. (US 20130209427 A1), evidenced by Orciani et al. (Skin Pharmacology and Physiology, 2010) and Al-Nbaheen et al. (Stem Cell Reviews and Reports, 2013).
Regarding claims 1-2, 6-7, and 10-12: Lee et al. teach a method for collecting mesenchymal stem cells (which read on “stem cells”) from synovial membrane (See Abstract). Synovial tissue is mixed with or injected into a hydrogel (which reads on “encapsulating… tissue in a hydrogel”), which is then cultured in a medium (See page 5, ¶11 and page 6, full ¶4-5). Stem cells that have migrated from the tissue and proliferated in the hydrogel can be isolated by enzymatic degradation (which reads on “decomposing”) of the hydrogel (See page 6, full ¶8). Lee et al. teach an embodiment wherein the hydrogel and tissue is cultured in media for 14 days (which reads on “3-20 days”) (See page 9, ¶4). The isolated mesenchymal stem cells can maintain their morphological characteristics (which reads on “a cell shape and a cell size”) through 15 passages (which reads on “until ninth subculture”) (See page 9, ¶7-8).
Lee et al. do not teach skin as the source of the mesenchymal stem cells.
Thangapazham et al. teach that mesenchymal stem cells can be isolated following migration out of skin explants (See ¶073, 0103, and 0232).
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 Lee et al. to use skin explants, such as are taught by Thangapazham et al., in place of synovial tissue. Combining prior art elements according to known methods to yield predictable results is considered to be prima facie obvious. See MPEP 2143(I)(A). Because Thangapazham et al. teach that mesenchymal stem cells can migrate from skin tissue (See ¶0103 and 0232) and Lee et al. teach that mesenchymal stem cells that have migrated out of a tissue can be captured and proliferated in a hydrogel that is subsequently degraded (See page 6, ¶4-5 and 8), one of ordinary skill in the art would have been sufficiently motivated to combine those teachings with a reasonable expectation of success for isolating skin-derived mesenchymal stem cells.
Regarding claims 5 and 8: Following the discussion of claims 1-2, 6-7, and 10-12, Lee et al., modified by Thangapazham et al., render obvious the use of a degradable hydrogel for capturing skin-derived mesenchymal stem cells but do not expressly teach the surface markers expressed by the cells. However, skin-derived mesenchymal cells inherently express CD29, CD44, CD73, CD90, and CD105 but not CD14, CD34, and CD45 (See Orciani et al., page 127, col. 1, full ¶2 and col. 2, ¶1; Al-Nbaheen et al., page 36, col. 1, ¶2).
Claims 1-2, 5-7, and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (WO 2020067774 A1, machine translation), in view of Thangapazham et al. (US 20130209427 A1), evidenced by Orciani et al. (Skin Pharmacology and Physiology, 2010) and Al-Nbaheen et al. (Stem Cell Reviews and Reports, 2013), further in view of Phillips et al. (International Wound Journal, 2013), Sellheyer et al. (Journal of the American Academy of Dermatology, 2010), and Akomeah et al. (European Journal of Pharmaceutical Sciences, 2004).
The teachings of Lee et al., Thangapazham et al., Orciani et al., and Al-Nbaheen et al. and are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 3: Following the discussion of claims 1-2, 4-7, and 9-12, Lee et al., modified by Thangapazham et al., evidenced by Orciani et al. and Al-Nbaheen et al., render obvious a method for isolating mesenchymal stem cells migrating out of skin tissue using a degradable hydrogel but do not teach pretreatment of the skin tissue.
Phillips et al. teach sterilization of porcine skin explants by submersion in PBS comprising hypochlorous acid and Tween 80 (which reads on “surfactant”) for 5 min (which reads on “1 to 10 minutes”), exposure to chlorine gas, resubmersion in PBS with hypochlorous acid and Tween 80, and washing with PBS (See page 49, col. 1, full ¶2).
Sellheyer et al. teach that the dermis is the primary reservoir of stem cells in the skin and that harvesting of the dermis could allow for the isolation and propagation of its stem cells for therapeutic use (See Abstract; page 860, col. 2, full ¶1; and page 861, col. 2, ¶1).
Akomeah et al. teach separation of the epidermis and dermis in human skin samples by immersion in water at 60°C (which reads on “50°C to 70°C”) for 45 s (which reads on “30 to 90 seconds”) (See page 338, col. 2, full ¶1).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date to modify the method rendered obvious by Lee et al., modified by Thangapazham et al., evidenced by Orciani et al. and Al-Nbaheen et al., to comprise the method taught by Phillips et al. for sterilizing skin explants. One would also be motivated to remove the epidermis from the dermis, as taught by Akomeah et al., because Sellheyer et al. teach that it comprises the majority of the skin’s stem cells and suggest that harvesting of the dermis specifically can be performed for isolating its stem cells (See Abstract; page 860, col. 2, full ¶1; and page 861, col. 2, ¶1). Both protocols could be readily performed prior to the method of Lee et al., modified by Thangapazham et al., evidenced by Orciani et al. and Al-Nbaheen et al.
Conclusion
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.
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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.
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
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