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
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 25 May 2023. It is noted, however, that applicant has not filed a certified copy of the CN202310597186.2 application as required by 37 CFR 1.55.
Specification
The use of the terms TrypLE™ and Accutase™, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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 Interpretation
The claims recite the term “digestive juice” which is interpreted as a solution comprising digestive enzymes because the term is not specifically defined by the instant specification.
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 5-7 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.
Claims 5 and 6 contain the trademark/trade name TrypLE™ and ACCUTASE™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a cell dissociation agent and, accordingly, the identification/description is indefinite.
Regarding claims 7, the phrase "and the like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "or the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al. (WO2022/142046, published 07 July 2020) as evidenced by Schlabe et al. (Burns 34, 2008) and Anbar et al. (Journal of Cosmetic Dermatology 19, 2020).
Since WO2022/142046 is not published in English, US2024/0052308 was used as a translation.
Regarding claim 1, Sun et al. teach isolated scalp tissue is pretreated with a digestive enzyme solution in a low temperature environment; the hair follicles (epidermal cells) can be effectively dissociated by digestion with the digestive enzyme solution at 30-37°C (Abstract). Sun et al. teach the preparation method wherein a sterilized biological safety cabinet (sterile environment) is used and a fresh isolated human scalp tissue is placed in a petri dish (culture dish) (para. [0044]-[0048]). Sun et al. teach prior to the initial digestive enzyme solution, a human scalp pretreatment: in a sterile environment, the isolated scalp tissue blocks are cut into blocks with a size of 0.1 – 0.2 cm2 (para. [0016]). Sun et al. teach as part of the disinfection treatment, lumps of scalp tissue are washed in PBS (para. [0017]). Sun et al. teach a method of making a human scalp hair follicle single cell suspension (epidermal cell suspension) wherein, the tissue is disinfected, treating with digestive enzyme solution (soaking skin tissues in a digestive juice) wherein the tissue is submerged at 2-8°C (low-temperature digestion) for 1-1.5 hours, then transferred to a thermostatic oscillator at 30-37°C (high-temperature digestion) for 1 hour, followed by the dissociated hair follicles are digested with pancreatin-EDTA to obtain a human scalp hair follicle single cell suspension, wherein the digestive process takes approximately 3 hours (para. [0010]-[0014] and fig. 1).
While human scalp hair follicles comprise a complex structure with both epidermal and dermal components the outer layers of a hair follicle are composed of epidermal cells as evidenced by Schlabe et al. Schlabe et al. disclose the hair follicle is a self-renewing adjunct to skin, which contains an epidermal and a mesenchymal component and the outer root sheath (ORS) of the hair follicle is equivalent to the basal epidermal layer and contains a subpopulation of multipotent stem cells in the bulge region (p. 377, 1st column). The hair follicle is essentially an invagination of the epidermis into the dermis, meaning it is a pocket formed by the epidermis going down into the skin. Therefore, the hair follicle cells read as epidermal cells. Additionally, the method of Sun et al. would result in separation of all cells into individual cells which would facilitate cell suspension of any skin tissue cell.
The statement in claim 1 in line 14, following “capable”, read as intended results. Intended results are not considered limiting because if the art teaches the steps of the method they would necessarily result in the same outcome. However, if the statement were considered limiting, Sun et al. teach the method disclosed is used to prepare a human scalp hair follicle single cell suspension with a large number and high vitality wherein the number of available cells is greater than 106 and cell viability up to 87% (para. [0034] and Table 1). Since Sun et al. teach blocks with a size of 0.1 – 0.2 cm2, which would be approximately 5x107 cells/10 cm2, therefore, the cell extraction amount is greater than 1x107 cells/10 cm2. Sun et al. teach the digestive process takes approximately 3 hours (fig. 1), which reads as within 4 hours.
Sun et al. teach washing the tissue and resuspending cells in PBS solutions, however, Sun et al. is silent to washing the skin tissue with normal saline and resuspending the epidermal tissues with normal saline to obtain the epidermal cell suspension (claim 1, steps 1 and 4).
However, both PBS and normal saline are both isotonic solutions and normal saline could be used as an alternative to PBS when isolating epidermal tissue, because normal saline is a well-known solution used with epidermal tissue and a well-known alternative to PBS in tissue handling, specifically epidermal tissue, as evidenced by Anbar et al. (p. 2686, 2nd column).
Therefore, it would have been obvious to substitute normal saline in place of PBS in the method of Sun et al. to achieve predictable result of extracting epidermal cells from skin tissue. Substitution of one known method for another known method, the methods having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 550 US 398 (US 2007) 82 USPQ2d 1385. Therefore, the claim steps of washing the tissue and resuspending cells in normal saline solutions are considered prima facie obvious over the prior art.
Regarding claims 2 and 3, Sun et al. teach treating the scalp tissue with a digestive enzyme solution (soaking skin tissues in a digestive juice) wherein the tissue is submerged at 2-8°C (low-temperature digestion) for 1-1.5 hours, then transferred to a thermostatic oscillator at 30-37°C (high-temperature digestion) for 1 hour (para. [0010]-[0014] and fig. 1). Since 2-8°C is between 0-10°C and 1-1.5 hours is between 0.1 and 8 hours and 30-37°C is between 25-40°C and 1 hour is between 0.1-8 hours, Sun et al. teach the limitations of claims 2 and 3.
Regarding claim 4, Sun et al. teach the tissue used in the method is human scalp tissue (para. [0016]).
Regarding claim 5, Sun et al. teach the digestive enzyme solution refers to a mixture of dispase solution and collagenase solution (para. [0026]). Sun et al. teach the pancreatin-EDTA refers to 0.25 g pancreatin powder and 0.02 g EDTA (ethylenediamine tetraacetic acid) are completely dissolved in a 100 ml PBS solution (para. [0029]).
Regarding claim 6, Sun et al. teach a dispase solution with a mass percentage concentration of 1%-3% and a collagenase solution with a mass percentage concentration of 1%-3% are mixed to obtain the digestive enzyme solution (para. [0015]). Sun et al. teach 0.5-1.5% digestive enzyme solution is used for short-term pretreatment of the isolated human scalp tissue at low temperature (2-8°C) and then 0.5-1.5% digestive enzyme solution digests the tissue at 30-37°C (para. [0034]). Sun et al. teach the dissociated hair follicles are transferred to 0.25-0.5% pancreatin-EDTA to completely dissociate the hair follicles (fig. 1). The EDTA percentage 0.25-0.5% falls within the required range of 0.01-10% EDTA of the claim limitation.
Regarding claim 7, the statement, “wherein the epidermal cells are used for clinical research or treatment of bums, scalds, pigmentation and hypopigmentation, ulcers, aesthetic dermatology and the like.”, is an intended use statement. Intended use statements do not limit the method for extracting epidermal cells because there are no active steps. Therefore, this claim is interpreted the same as claim 1 and is rejected for the same reasons.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Relevant prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Tait et al. (Scientific Reports, 2021)
Tait et al. teach engineered epithelial cell sheets for clinical replacement of non-functional upper aerodigestive tract mucosa. Tait et al. teach the biopsy is incubated overnight at 4°C, epithelial sheet removed using forceps. The epithelial sheet is minced then placed into TrypLE Express and incubated for 30 minutes at 37°C.
Gibco by Life technologies (Collagenase manual, 2013)
Gibco teaches the recommends using Type I collagenase to dissociate epithelial tissue at a concentration of 50-200 U/mL (or 0.1-0.5% W/V).
Gibco by Life technologies (Dispase manual, 2013)
Gibco teaches dispase should be diluted to a final concentration of 0.6-2.4 U/mL for tissue dissociation, noting more efficient dissociation of tissue is obtained by mixing the Dispase at 0.3-0.6 U/mL with collagenase at 60-100 U/mL.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICHOLAS A. HUMPHRIES whose telephone number is (703)756-5556. The examiner can normally be reached Monday - Friday, 7:30am - 4:30 pm.
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, James Schultz can be reached at 571-272-0763. 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.
/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631