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
This application was filed 25th of March 2024 and is a 371 application of PCT/JO2021/050015 filed on 23rd of Sept. 2021.
Election/Restrictions
In the response filed on the 2nd of July 2026, Applicant’s elected Group II, claims 3-5, drawn to a method of obtaining stem cells obtained from apical papilla tissue of impacted third molars of a subject with traverse.
Applicant's election with traverse is acknowledged. The traversal is on the ground(s) that that unity of invention does exist between Groups I to II because there is a technical relationship that involves the same special technical feature, and the technical feature that defines the contribution which each of the groups, taken as a whole, makes over the prior art (Remarks, page 3). This is not found persuasive because the examiner was able to provide art which satisfied the limitations of product of group I, thereby demonstrating that the special technical feature lacks novelty.
The requirement is still deemed proper and is therefore made FINAL.
Group II, claims 3-5, drawn to a method of obtaining stem cells obtained from apical papilla tissue of impacted third molars of a subject.
Claims 1-2 directed to Group I are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Claim Status
Currently, claims 3-5 are under consideration in this office action.
Information Disclosure Statement
It is noted that the information disclosure statements (IDS) submitted on 2nd of July 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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. Further, Applicants are reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability.
Specification
The disclosure is objected to because of the following informalities: There is a line through paragraph 11 on page 3. Further, it appears that the specification does not a disclosed “Example 3”. The specification lists Examples 1-2 on page 11 and then Example 4 on page 12. It is noted that this is also the case in the filed PCT/JO21/50015 application. It is unclear if Example 3 is missing or just not present seems in the specification. Appropriate correction is required.
The use of the terms: Essential 8, page 3; Advanced DMEM, page 8, Gibco, page 8, 14, 15; Accutase, page 11; FACS Jazz, page 11; GlutaMAX, page 11; BD Biosciences, page 11-12; Zeiss, pages 12-13, 16; ThermoFisher Scientific, pages 12 and 15; Axiovert, pages 12-13 and 16; Corning pages 12 and 14; Biowest, page 15; Sigma, pages 15-16. 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.
Appropriate correction is required.
Claim Objections
Claim 3 is objected to because of the following informalities: grammar/typos. Claim 3 appears to be missing a comma after “glutamine” and before “penicillin.” Claim 3 recites the limitation "the cultured fragmented tissue" in line 7. However, it is suggested that the claim recite “cultured the fragmented apical papilla tissue” since line 4 recites “a fragmented apical papilla tissue”, therefore, for consistency it is clear what “fragmented tissue” is being referred to in the claim. Further, Claim 3, line 10 and 11, and Claim 4 lines 1 and 3, appear to be missing the word “tissue” after the claim recites “apical papilla.”
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 3 and 5 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 3 and 5 contains the trademark/trade name “Essential 8” Flex media (see claim 3, line 4, and claim 5, line 2. 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 the media that the stem cells/pluripotent stem cells populations are cultured/maintained in the method of obtaining stem cells and, accordingly, the identification/description is indefinite.
Claim 3 recites “obtaining extracted third molars from a subject, followed by isolating the apical papilla tissue from the impacted third molars” (lines 2-3). Claim 3 recites the limitation “the impacted third molars” in line 3, but the claim does not require that the extracted third molars of the subject be “impacted”. It is unclear to a person of ordinary skill in the art that the isolated third molar of the subject is the impacted third molar from the subject. Thus, there is insufficient antecedent basis for this limitation.
Claim 3 recites “obtaining extracted third molars from a subject, followed by isolating the apical papilla tissue from the impacted third molars; culturing a fragmented apical papilla tissue in a plate” (lines 2-4). The claim 3 recites the imitations of “a fragmented apical papilla tissue”, which has insufficient antecedent basis, because claim 3 recites “isolating the apical papilla tissue” in line 2, and does not refer to the apical papilla tissue as being “fragmented”. Thus, it is unclear to a person of ordinary skill in the art that the fragmented apical papilla tissue is the isolated apical papilla tissue. Further, it is noted that the specification recites “Extracted tissue was then minced into small pieces, and small fragments were maintained in two different types of culture medium; a maintenance medium for pluripotent stem cells (PSCs) and, another maintenance medium for mesenchymal stem cells (MSCs)” (spec. para. 87). Therefore, the specification is referring to the fragmented apical papilla tissue as being associated with a mincing step, rather than just an isolating step. For compact prosecution the claimed “fragmented” apical papilla tissue will be interpreted as an implicit step, and any apical papilla tissue obtained from the isolation step will be examined as the “fragmented” apical papilla tissue.
Appropriate correction is required.
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 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Bowermaster et al., (US2009/0130753 A1, published 2009, cited IDS 7/2/2024, hereinafter as “Bowermaster”) in view of Truncale et al., (US8,834,928 B1, published 2014, cited IDS 7/2/2024, hereinafter as “Truncale”), Duaa Abuarqoub (Regenerative Medicine 2020, 3rd Global Conference on Tissue Engineering and Regenerative Medicine, published June 2020, hereinafter as “Abuarqoub 2020”), and Abuarqoub, et al., (Archives of oral biology 60.10: 1545-1553, published 2015, hereinafter as “Abuarqoub 2015”), Cheung et al., (US10,106,773 B2, published 2018, cited IDS 7/2/2024; hereinafter as “Cheung”), and Kerkis et al., (WO2014/141210 A2, published 2014, hereinafter as “Kerkis”) and Federico Ferro (US2011/0158962A1, published 2011, hereinafter as “Ferro”).
Regarding claim 3 and 5, Bowermaster discloses a method of obtaining the stem cells from tissue comprising the apical papilla (i.e. mesenchymal dental papilla) of third molars of a subject (see e.g. abstract, claims 1, 2, 4, fig. 6). Bowermaster discloses wherein the stem cells have pluripotent characteristics, which corresponds to the claim limitation that stem cells can be differentiated into an ectoderm, a mesoderm, and endoderm germ layers (i.e. pluripotent)(see e.g. background section), and wherein the stem cells are characterized by the presence of TRA-1-60 (i.e. TRA60-1), SSEA4, TRA-1-80 (i.e. TRA80-1) and OCT4 surface markers (see e.g. page 2, and claims 1-7). Bowermaster discloses obtaining extracted third molars from a subject (see e.g. page 3-4, para. 37, Example 1), followed by isolating the apical papilla tissue from the third molars (see e.g. page 3-4, Example 1). Bowermaster discloses culturing a fragmented apical papilla tissue in a bactericidal solution (see e.g. page 3-4, Example 1). Bowermaster discloses isolating stem cells from the obtained tissue followed by expanding the isolated stem cells, and isolating a mixture of stem cells from papilla (see e.g. page 3-4, Example 1). Further, Bowermaster discloses isolating a pure population of pluripotent stem cells from apical papilla (see e.g. page 3-4, Example 1, claims 1-7). Further, Bowermaster discloses that methods for sorting for pluripotent stem cells from apical papilla were known and available (i.e. fluorescence activated cells sorting, FACS)(see e.g. para. 21).
Although Bowermaster discloses that a majority of the stem cells are negative for TRA-1-60 (i.e. TRA60-1)(see e.g. para. 20).
Nevertheless, the prior art of Truncale discloses fluorescence activated cell sorting (i.e. FACS)(see e.g. col. 68, 224) and investigating the percentage of TRA-1-60 (see e.g. col. 35), which is known stem cell marker for stem cells of apical papilla (SCAPs) tissue, where the surface marker is known to differentiate into osteoblasts (see e.g. col. 33-36, sec. 2.4, and table 6).
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 of isolating pluripotent stem cells from apical papilla tissue, as taught by Bowermaster, and incorporate the apical papilla stem cell markers of TRA-1-60, as taught by Truncale, with a reasonable expectation of success because one of ordinary skill in the art would know that stem cells obtained from the apical papilla are multipotent stem cells that may be induced to differentiate into a variety of cell and tissue types (as taught by Bowermaster, see e.g. para. 20-21). Further, Truncale discloses that TRA-1-60 is known stem cell marker for stem cells of apical papilla (SCAPs), which have potential to differentiate to osteoblasts (see e.g. sec. 2.4, and table 6). Additionally, both Bowermaster and Truncale disclose using apical papilla tissue for methods of isolating stem cells, as discussed above. Thus, a person of ordinary skill of the art would have had predictable results with a reasonable expectation of success.
Bowermaster does not explicitly disclose that the third molar is impacted, a plate including essential 8 flex media and alpha modification of Eagle's Medium supplemented with glutamine, penicillin, streptomycin, amphotericin B, and platelet lysate, incubating the cultured fragmented tissue in a humidified incubator in a tissue culture well plate coated with vitronectin, and sorting for a pure population of pluripotent stem cells from apical papilla.
However, the prior art of Abuarqoub 2020 discloses isolating pluripotent stem cells with germinal differentiation potential (i.e. ectoderm, a mesoderm, and endoderm germ layers) from apical papilla (i.e. P-SCAP) of impacted third molars by culturing a fragmented apical papilla tissue in essential 8 flexTM media (see abstract, page 8).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to have combined the method of isolating pluripotent stem cells from apical papilla tissue, as taught of Bowermaster, to incorporate tissue comprising the apical papilla of impacted third molars of a subject by culturing in essential 8 flexTM media, as taught by Abuarqoub 2020, with a reasonable expectation of success because one of ordinary skill in the art would know apical papilla tissue is a source for stem cells that have pluripotent features and are able to express pluripotency markers (see Bowermaster and Abuarqoub 2020 e.g. backgrounds, respectively). Additionally, an artisan of ordinary skill in the art of isolating dental pluripotent stem cells has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007). In the instant case, both Bowermaster and Abuarqoub 2020 disclose using apical papilla tissue for methods of isolating stem cells, as discussed above. Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success of modifying the methods of Bowermaster and incorporating apical papilla tissue of impacted third molars of a subject, culturing in essential 8 flexTM media (see e.g. Abuarqoub 2020, see abstract, page 8).
Abuarqoub 2020 does not explicitly disclose that the media contains an alpha modification of Eagle's Medium supplemented with glutamine, penicillin, streptomycin, amphotericin B, and platelet lysate; incubating the cultured fragmented tissue in a humidified incubator in a tissue culture well plate, and sorting a pure population of pluripotent stem cells from apical papilla.
However, the prior art of Abuarqoub 2015 discloses culturing dental stem cells from apical papilla tissue with media that contains an alpha modification of Eagle's Medium supplemented with glutamine, penicillin, streptomycin, amphotericin B, and platelet lysate (PL)(see e.g. page 1546). Further, Abuarqoub 2015 discloses incubating the cultured fragmented tissue in a humidified incubator (i.e. 37°C in 5% Co2) in a tissue culture well plate (see e.g. page 1546). Further, Abuarqoub 2015 discloses sorting (e.g. flow cytometry) for a pure population of pluripotent stem cells from apical papilla (see e.g. page 1546, 1549, figs. 1-3).
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 method of isolating pluripotent stem cells from apical papilla tissue, as taught of Bowermaster, and incorporate media that contains an alpha modification of Eagle's Medium supplemented with glutamine, penicillin, streptomycin, amphotericin B, and platelet lysate, and cultures in a humidified incubator, on a well-place, and sorts for a pure population, as taught by Abuarqoub 2015, with a reasonable expectation of success because one of ordinary skill in the art would want to obtain a high density of pluripotent stem cells from apical papilla tissue (as taught by Abuarqoub 2015, see e.g. page 1549). Further, one of ordinary skill in the art would want to separate the undifferentiated cells in order to isolate a pure dental pluripotent populations of stem cells for therapeutic use as suggested by Bowermaster (see e.g. abstract, and page 2). Additionally, an artisan of ordinary skill in the art of isolating dental pluripotent stem cells has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007). In the instant case, both Bowermaster and Abuarqoub 2015 disclose using sorting techniques to obtain a pure population of pluripotent stem cells from apical papilla (see e.g. page 2 and 1548, respectively). Thus, a person of ordinary skill in the art would have wanted to modify the media, as taught by Bowermaster with the media modifications, as taught by Abuarqoub 2015, with a reasonable expectation of success because one of ordinary skill in the art would use platelet lysate (PL) to positively affect proliferation and differentiation of dental pluripotent stem cells (see e.g. page 1552).
Abuarqoub 2015 is silent regarding the use of a tissue culture well plate coated with vitronectin.
However, the prior art of Truncale discloses that stem cell interacting with vitronectin creates a nexus that promotes to osteogenic differentiation (see e.g. col. 14). Additionally, the prior art of Cheung discloses plating cells from apical papilla dental tissues (i.e. isolated pluripotent stem cells) and culturing on a well coated plate with vitronectin (see e.g. abstract, col. 13).
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 of isolating pluripotent stem cells from apical papilla tissue, as taught of Bowermaster, and incorporate of a tissue culture well plate coated with vitronectin, as taught by Truncale and Cheung, with a reasonable expectation of success because one of ordinary skill in the art would want to isolate a substantially homogenous population of pluripotent stem cells from apical papilla tissue (e.g. periodontal ligament, as taught by Cheung, see e.g. abstract; and Bowermaster, see. e.g. page 15).
Regarding claim 4, as stated supra, the prior art of Truncale discloses fluorescence activated cell sorting (i.e. FACS)(see e.g. col. 68, 224) and investigating the percentage of TRA-1-60 (see e.g. col. 35), which is known stem cell marker for stem cells of apical papilla (SCAPs) tissue, where the surface marker is known to differentiate into osteoblasts (see e.g. col. 33-36, sec. 2.4, and table 6).
Bowermaster et al., does not explicitly disclose sorting the pluripotent stem cells for a percentage of TRA-1-60 surface marker positive population.
However, the prior art of Kerkis discloses isolating and sorting (i.e. Flow cytometry) immune dental pulp stem cells (i.e. IDPSC) from apical papilla (i.e. dental pulp tissue) for a percentage of 2-30% TRA-1-60 (i.e. TRA1-60) surface marker positive population (see e.g. pages 37-38, 42, 104-105, 113, 144, 150, claims 32-87, and Examples 15, 21, 25). Additionally, the prior art of Ferro discloses isolation of pulp marrow similar cells (i.e. DPMSCs) expressing Oct-4 and Nanog combined with SSEA-4, SSEA-3, TRA-1-60 correlated with presence of the most primitive cells in DPMSC cultures (see e.g. para. 254-259).
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 of isolating pluripotent stem cells from apical papilla tissue, as taught of Bowermaster, and incorporate of a percentage of TRA-1-60 surface marker positive population, as taught by Truncale, Kerkis, and Ferro, with a reasonable expectation of success because one of ordinary skill in the art would know that the TRA1-60 is used to obtain a high percentage of pluripotent stem cells (as taught by Kerkis, see e.g. page 150). Further, a person of ordinary skill in the art would have had a reasonable expectation of success because one would know that pluripotent stem cells from apical papilla tissue express surface marker TRA-1-60 and that the cell population has research and therapeutic potential for a variety of research purposes, such as differentiation to osteogenic lineage (see e.g. Bowermaster page 1 and 3 and Kerkis page 107 and 136). Thus, providing motivation to do.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 10AM - 5:00PM (EST).
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JOSEPHINE GONZALES
Examiner
Art Unit 1638
/JOSEPHINE GONZALES/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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