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 1-13, of record 6/24/2024, are pending and subject to prosecution.
Priority
The instant application is a national stage entry of PCT/KR2022/021214 (filed 12/23/2022). Acknowledgement is made of the applicant’s claim for foreign priority to Republic of Korea application 10-2021-0187682 (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 ¶0109 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, 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.
In ¶0116 of the application’s PG Pub, “Denhart’s soln” should be replaced with “Denhardt’s solution”, and “’X TED” should be clarified.
Claim Objections
Claim 1-6 are objected to because of the following informalities:
In line 5 of claim 1, “obtained” should be deleted.
In claims 2 and 4-5, “step” should be deleted. Additionally, in line 2 of claim 5, “a hair follicle tissue is” should be rewritten as “two or more hair follicle tissues are”.
In line 2 of claim 3, “a should be inserted in front of “follicular”.
Claim 6 should be rewritten to recite “one or more genes selected from the group consisting of SANP25, COL10A1, TMEM119, AQP1, PLCB4, and ITGA8” to form a proper Markush grouping.
Appropriate correction is required.
Claim Interpretation
Claim 2 recites the limitation “encapsulating a hair follicle tissue in a double-layered hydrogel”. The term “double-layered” is interpreted as requiring that the hydrogel comprise top and bottom layers, consistent with ¶0042 of the application’s PG Pub, or that the hydrogel comprise outer and inner layers.
Claims 8-12 recite the limitation “hair follicle-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 hair follicle-derived stem cells.
Claims 11-13 also recite a pharmaceutical, quasi-drug, or cosmetic composition for hair loss improvement or hair growth promotion comprising hair follicle-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 hair follicle-derived stem cells as an active ingredient, the broadest reasonable interpretation of the compositions is considered to encompass hair follicle-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 5-6 and 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites the limitation “an inter-tissue spacing of 1 mm or more and 50 mm or less”. It is unclear whether the claimed spacing is 1-50 mm, 1 mm to an undefined limit, or 0-50 mm.
The term “increased” in claims 6 and 9 is a relative term which renders the claims indefinite. The term “increased” 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 to what the expression of SANP25, COL10A1, TMEM119, AQP1, PLCB4, or ITGA8 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.
Claims 8 and 10-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Regarding claims 8 and 10-13: Claims 8 and 10 are directed to hair follicle-derived stem cells prepared by the method according to claim 1. Claims 11-13 are directed to a pharmaceutical, quasi-drug, or cosmetic composition comprising hair follicle-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 hair follicle-derived stem cells. Based upon this interpretation, the claims are analyzed as follows:
Step 1: The claims are directed to compositions comprising hair follicle-derived stem cells, which are a statutory category of matter (Step 1: YES).
Step 2A, prong 1: Hair follicle-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 hair follicle-derived stem cell is a naturally occurring hair follicle-derived stem cell. Vasyliev et al. teach a population of neural crest-derived stem cells in hair follicles that express CD73, CD90, CD105, and Nestin but do not express CD34, CD45, and HLA-DR (See Abstract). Scannell et al. teach that neural crest-derived stem cells express Lgr5 (See Abstract; page 4, col. 2, ¶1-2; and page 5, col. 1, ¶1), and Boddupally et al. teach a Lgr5+ stem cell population in hair follicles (See page 721, col. 1, full ¶1 and page 722, col. 2, ¶1). The claimed cells appear to 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 8 and 10-13 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 8 and 10-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vasyliev et al. (Experimental Oncology, 2017), evidenced by Scannell et al. (Frontiers in Oncology, 2013) and Boddupally et al. (Stem Cells, 2015).
Regarding claims 8 and 10-13: Vasyliev et al. teach the isolation of a population of neural crest-derived stem cells from hair follicles for regenerative use (which reads on “pharmaceutical composition”, “quasi-drug composition”, and “cosmetic composition”) (See Abstract). The cells express CD73, CD90, CD105, and Nestin and do not express CD34, CD45, and HLA-DR (See Abstract). Vasyliev et al. do not expressly teach whether the cells are also Lgr5+. However, Scannell et al. teach that neural crest-derived stem cells express Lgr5 (See Abstract; page 4, col. 2, ¶1-2; and page 5, col. 1, ¶1), and Boddupally et al. teach a Lgr5+ stem cell population in hair follicles (See page 721, col. 1, full ¶1 and page 722, col. 2, ¶1), which indicates that the neural crest-derived hair follicle stem cells taught by Vasyliev et al. would also be expected to express Lgr5, thereby anticipating the claimed invention.
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. The 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, 4-5, 7-8, and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Vasyliev et al. (Experimental Oncology, 2017), evidenced by Scannell et al. (Frontiers in Oncology, 2013) and Boddupally et al. (Stem Cells, 2015), in view of Lee et al. (WO 2020067774 A1, machine translation).
The teachings of Vasyliev et al., Scannell et al., and Boddupally et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 1-2, 4, and 7: Following the discussion of claims 8 and 10-13, Vasyliev et al., evidenced by Scannell et al. and Boddupally et al., teach the isolation of a population of neural crest-derived stem cells from hair follicles. Vasyliev et al. teach that hair follicles (which read on “a hair follicle tissue”) were removed from human skin specimens and explanted over a thin layer of collagen gel (See page 172, col. 2, full ¶1). Stem cells emigrated from the explant and proliferated on the gel substrate (See page 174, col. 1, ¶1). Vasyliev et al. do not teach the encapsulation of the hair follicle in a degradable hydrogel.
Lee et al. teach an efficient method for collecting stem cells from synovial membranes (See Abstract). Synovial tissue is mixed with, injected into, or otherwise incorporated in 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). The hydrogel can comprise polymers such as collagen (See page 6, full ¶3). 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).
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 Vasyliev et al., evidenced by Scannell et al. and Boddupally et al., to comprise the use of a degradable hydrogel, as taught by Lee et al., for capturing, proliferating, and isolating neural crest-derived stem cells from hair follicles. One would have been motivated to make this modification because Lee et al. teach that it enables the efficient extraction of stem cells from tissue (See Abstract and page 8, ¶6). There would be a reasonable expectation of success in doing so because explanted hair follicles could be readily incorporated into or covered with additional collagen gel (which would read on “encapsulating… in a double-layered hydrogel”) so that stem cells could be isolated in the same manner as synovial tissue stem cells.
Regarding claim 5: Following the discussion of claims 1-2, 4, 7-8, and 10-13, Vasyliev et al. teach the explantation of hair follicles in Petri dishes but do not expressly teach the spacing of the follicles. However, Vasyliev et al. show that stem cell outgrowth from a explant just before passaging extended at least 300-500 µm around the explant (See fig. 1a), which suggests that multiple explants be spaced at least 1 mm apart (which would read on “1 mm or more” and “50 mm or less”) in order to maximize outgrowth.
Claims 1, 3-4, 8, and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Amoh et al. (Cell Cycle, 2012) in view of Lee et al. (WO 2020067774 A1, machine translation).
Regarding claims 1, 3-4, 8, and 11-13: Amoh et al. teach the culture of Nestin-expressing stem cells derived from hair follicles (See Abstract). Rat whisker follicles were separated into upper (which reads on “a hair follicle tissue” and “a fragment obtained by removing a site corresponding to follicular infundibulum from epidermis”), middle, and lower parts and cultured in DMEM containing 1% methylcellulose (which read on “encapsulating… in a hydrogel”) until the stem cells formed spherical colonies (See fig. 2). Amoh et al. do not teach the encapsulation of the hair follicle in a degradable hydrogel.
Lee et al. teach an efficient method for collecting stem cells from synovial membranes (See Abstract). Synovial tissue is mixed with, injected into, or otherwise incorporated in 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).
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 Amoh et al. to comprise the use of a degradable hydrogel, as taught by Lee et al., for capturing, proliferating, and isolating stem cells from hair follicle fragments. One would have been motivated to make this modification because Lee et al. teach that it enables the efficient extraction of stem cells from tissue (See Abstract and page 8, ¶6). There would be a reasonable expectation of success in doing so because hair follicle fragments could be readily incorporated into a degradable hydrogel so that stem cells could be isolated in the same manner as synovial tissue stem cells.
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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