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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on December 23, 2025. Claims 21-23, 25 have been amended. Claims 1-5 and 8-17 have been canceled.
Election/Restrictions
Applicant's election without traverse of Group II, claims 6-7, drawn to a method of isolating chorionic MSCs that are not from the tips of the villi, by cutting out these cells from the desired region of the chorion, i.e., avoiding the tips of the villi, and by somehow obtaining (isolating or separating away) these cells, in the reply filed on April 23, 2025, was previously acknowledged.
Since searches for the elected Group II rendered results for Groups I and III, the restriction requirement between Groups I-III is hereby withdrawn, and Groups I and III are hereby rejoined with the elected group.
In addition, Applicants' election of the following species without traverse, in the reply filed on July 7, 2025, was previously acknowledged:
A species of CD321 being absent (claim 7).
A species of CD49e being present (claim 19)
A species of hyaluronic acid (claim 24),
A species of cartilage (claim 26),
A species of hyaline cartilage (claim 27),
A species of articular cartilage (claim 28) and arthritis (claim 29),
Upon further consideration, the species election requirement is withdrawn, and all species are rejoined and examined together. The restriction requirement as set forth in the Office actions mailed on 02/28/2025 and 05/02/2025 are hereby withdrawn.
In view of the above noted withdrawal of the restriction requirement between Groups I-III and species election requirement, applicants are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Therefore, claims 6-7 and 18-29 are currently under examination.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/KR2020/012417, filed September 15, 2020, which claims priority to
Republic of Korea Application KR10-2019-0115322, filed on September 19, 2019, is acknowledged.
Filing on March 18, 2022, of certified untranslated copy of the Republic of Korea publication KR10-2019-0115322 filed on September 19, 2019, is acknowledged. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 3 7 CFR 41.154(b) and 41.202( e ). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Thus, priority date is not yet perfected, and the earliest possible priority for the instant application is September 19, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 18, 2022 was previously acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Withdrawn Claim Rejections -35 USC§ 112(b)
In view of Applicants' amendment to claims 21-23 and 25, the rejection of claims 21-23 and 25 under 35 U.S.C. 112(b) is moot and has been withdrawn.
Withdrawn Claim Rejections -35 USC§ 103
In view of Applicants amendment to the instant claims, amending claims 21-22 and 25, the rejection under 35 U.S.C. 103 to claims 6 and 20-22 and 25-29 as being unpatentable over Ha et al. (US 2016/0324901 A) has been withdrawn. A response to Applicant's arguments with regard to a withdrawn rejection is moot. A response to Applicant's arguments pertinent to a new or remaining rejection can be found below.
***
In view of further considerations and the identification if allowable subject matter, the rejection under 35 U.S.C. 103 to claims 7 and 19 as being unpatentable over Ha et al. (US 2016/0324901 A), in view of Ferreira et al. (Stem Cell Res Ther. 2018 Feb 5;9(1):28.; cited in Applicant’s PCT application and IDS), and further in view of Muench et al. (Development. 2017 Apr 15;144(8):1399–1411.), has been withdrawn. A response to Applicant's arguments with regard to a withdrawn rejection is moot. A response to Applicant's arguments pertinent to a new or remaining rejection can be found below.
***
In view of further considerations and the identification if allowable subject matter, the rejection under 35 U.S.C. 103 to claims 7 and 19 as being unpatentable over Ha et al. (US 2016/0324901 A), in view of Ferreira et al. (Stem Cell Res Ther. 2018 Feb 5;9(1):28.; cited in Applicant’s PCT application and IDS), Muench et al. (Development. 2017 Apr 15;144(8):1399–1411.), Sugano et al. (Blood. 2008 Feb 1;111(3):1167-72. Epub 2007 Nov 6.), and Denk et al. (Mediators Inflamm. 2015:2015:463950. doi: 10.1155/2015/463950. Epub 2015 Oct 18.), has been withdrawn. A response to Applicant's arguments with regard to a withdrawn rejection is moot. A response to Applicant's arguments pertinent to a new or remaining rejection can be found below.
Claim Objections
Claim 19 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
New Claim Rejections - 35 USC § 103
Claims 6, 18, 20-29 are rejected under 35 U.S.C. 103 as being unpatentable over Ha et al. (citation to US 10,232,000 B2, prior published US 2016/0324901 A1), in view of Pelekanos et al. (J Vis Exp. 2016 Jun 6:(112):54204.), and Edinger et al. (US 2008/0152629 A1). This is a new rejection necessitated by Applicants' amendments to the claims, such as amending claims 21-23 and 25, in the response filed on December 23, 2025.
Regarding claims 6, 18 and 20-21, Ha teaches a method of isolating placental stem cells from a specifically selected portion of placental chorionic tissue. Ha further teaches the “basal portion of chorionic trophoblast layer,” or bCT, as a tissue layer generally about 5-6 mm thick and corresponding to approximately 20-30% of the portion adjacent to the chorionic membrane of the total chorionic trophoblast layer positioned between the chorionic membrane and decidua (column 5, para. 1-2; column 6, para. 2-4; claim 1-5). Ha teaches that stem cells are obtained from the isolated bCT by enzymatic treatment followed by recovery and screening of adherent stem cells (column 5, lines 15-29; column 8, lines 1-25; claims 1 and 5-7).
Ha’s Example 1 specifically taches removing the amniotic membrane and then carefully isolating, using sterilized forceps and a knife, a tissue portion corresponding to approximately of the region adjacent to the chorionic membrane, washing the tissue, digesting it with a collagenase, filtering and culturing the recovered cells, and obtaining stem cells by screening cells attached to the culture container bottom (column 7-8, bridging para.). Therefore, Ha tacehs selection of a defined shallow chorionic-side placental region, cutting of the region, and obtaining stem cells.
Ha does not expressly teach or characterize the selected tissue as the specific chorionic-villus portion measured from the chorionic plate toward the distal villi.
However, Pelekanos teaches the anatomical relationship, specially that the placenta can be dissected into the decidua, chorionic villi, and chorionic plate, and that MSC can be separately isolated from each dissected region (Abstract). Pelekanos further teaches that the branched placental villi converge onto the fetal chorionic plate (pg. 1, para. 1-4). Pelekanos expressly teaches that the placenta is a fetomaternal organ and that the chorionic villi and chorionic plate are fetal tissues, and further teaches isolation of MSC from the dissected chorionic-villus region (pg. 4, Section 9.1; pg. 6, para. 3; Fig. 1). Pelekanos teaches mechanically removing the amniotic membrane while leaving the chorionic plate intact, cutting pieces approximately 1 cm wide by 0.5 cm deep from the chorionic plate, and dissecting chorionic-villus tissue approximately 1 cm2 by 0.5-1 cm deep from placental tissue where the chorionic plate has already been removed. Pelekanos also teaches mincing the isolated CV tissue and enzymatically digesting it for MSC isolation (pg. 3, Sections 2-5). Thus, Pelekanos teaches cutting a controlled-depth portion of chronic villi directly underlying the chorionic plate and thereafter obtaining MSC from the dissected villous tissue.
Before the effective filing date, the person of ordinary skill in the art would have found it obvious to apply Ha’s teaching of selecting a shallow, defined fractional chorionic-side tissue region to the chorionic-villus dissection taught by Pelekanos. The teachings of Ha and Pelekanos are both directed to obtaining placental MSC by controlling the anatomical source tissue, and Ha demonstrates that cells isolated from different placental subregions possess different proliferation, differentiation, and tissue-regenerative properties. Thus, the ordinary artisan would have found it obvious to control the depth and anatomical location of the tissue used for stem-cell isolation. The ordinary artisan would have been motivated to isolate a shallow chorionic-plate-adjacent portion of the villi taught by Pelekanos using the limited proximal distance, as taught by Ha, to obtain a more specially defined placental stem cell population and to obtain the advantageous properties taught to vary with placental tissue source.
Specifically, regarding the recitation of “1/3 point of the whole thickness,” Ha teaches selection of the adjacent 20-30% tissue region, identifying 25% in examples. Ha states:
“Under such circumstances, the present inventors have made intensive studies to develop stem cells having more excellent stem cell capacity from the stem cells derived from the placenta. As a result, present inventors have completed the present disclosure by isolating a basal portion of chorionic trophoblast layer (bCT) which is a tissue layer corresponding to a thickness of about 25% as a portion adjacent to a chorionic membrane in a total chorionic trophoblast layer (tCT) of the placenta to prepare stem cells derived from the basal portion of chorionic trophoblast layer and verifying that the stem cells derived from the basal portion of chorionic trophoblast layer (bCT) which is a part of the tissues of the placenta exhibit uniform growth characteristic, and superb proliferation and differentiation characteristics as pluripotent stem cells, as compared with the conventional stem cells derived from the whole placenta or other tissues, and exhibit an excellent tissue regeneration effect in a tissue defect animal model.” (column 2, para. 3)
and,
“The collected placenta was put in a sterile container and then transferred, an amniotic membrane was removed from the transferred placenta tissue, and then a basal portion of chorionic trophoblast layer tissue which corresponds to a thickness of about 25% of an adjacent (close) portion to the chorionic membrane of the total chorionic trophoblast layer (tCT) positioned between a chorionic membrane (CM) and decidua (DC) was carefully isolated by using sterilized forcep W and knife.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955). In the instant case selection of a proximal villous region extending to approximately 1/3 of the villous depth would have amounted to no more than optimization of the known tissue-selection depth, in view of Ha’s teachings that biological properties depend upon the particular placental subregion selected.
Regarding step 3), of claim 18, the combined teachings of Ha and Pelekanos are applied, as above. Ha in view of Pelekanos teaches steps 1) and 2). Ha teaches that the placental stem cells may be used in treatment protocols involving engrafting, transplanting, or infusing the stem cells into tissues or organs of the body, wherein the cells may form new or changed tissue or reinforce existing tissue (column 6, para. 6-8). Ha further teaches the method of transplanting the stem cells from basal portion of chorionic trophoblast layer in a patient in need of a cellular therapeutic agent and teaches the treatment of patients having cartilage damage, cartilage defect, bone defect, tendon-ligament defect, or fat tissue defect (column 6, para. 3 through column 7, para. 4; Example 8; Fig. 13-14; claims 8-9).
Furthermore, the ordinary artisan would have recognized the prior art teaches administration of placental stem cells for regenerative purposes, further in view of Edinger. Edinger teaches administration of placental stem cells to an individual in need of stem cells, including injection into damaged organs for organ neogenesis and repair of injury (Abstract; [0224]). Hence, the ordinary artisan would have found it obvious to administer the stem cells obtained, as taught by Ha and Pelekanos, to an individual in need thereof for the known therapeutic purpose as taught by Ha and Edinger.
Regarding claim 22, the combined teachings of Ha, Pelekanos, and Edinger render claims 6 and 21 obvious. Edinger additionally teaches that the placental stem cells are injected into a damaged organ for neogenesis and repair, as well as injectable solutions for administration of cellular products ([0224]; [0250]).
Regarding claim 23, the combined teachings of Ha, Pelekanos, and Edinger render claims 6 and 21 obvious. Edinger additionally teaches that the placentally cells may be suspended in a hydrogel solution suitable for injection, and that the cell containing hydrogel may form a matric for implantation ([0257]).
Regarding claim 24, the combined teachings of Ha, Pelekanos, and Edinger render claims 6, 21, and 23 obvious. Edinger additionally teaches hydrogel forming materials including alginate, polyacrylates, and polyethylene oxide-polypropylene glycol block copolymers ([0257]).
Regarding claim 25, the combined teachings of Ha, Pelekanos, and Edinger render claim 6 obvious. Ha teaches a composition for regenerating tissues and transplantation of the stem cells to damaged tissue and further teaches that the transplantation amount is selected according to the subject, disease, dosage, route, and treatment period (column 7, para. 1-8). Additionally, Edinger teaches administration of placental stem cells to an individual for repair of injury in vivo ([0224]). Therefore, the ordinary artisan would have found it obvious to administer a therapeutically effective amount of the composition to a subject in need of tissue regeneration, with the effective amount selected according to obvious parameters, as taught by Ha.
Regarding claim 26, the combined teachings of Ha, Pelekanos, and Edinger render claims 6 and 25 obvious. Ha additionally taches regeneration and treatment involving cartilage, fat, bone, nerve, ligament, and tendon (column 7). Edinger also teaches use of placental stem cells for augmentation, repair, or replacement of cartilage tendon, or ligaments ([0237]).
Regarding claim 27, the combined teachings of Ha, Pelekanos, and Edinger render claims 6, 25, and 26 obvious. Ha additionally teaches that the cartilage can be hyaline cartilage, fibrocartilage, or elastic cartilage (column 7, lines 38-45).
Regarding claim 28, the combined teachings of Ha, Pelekanos, and Edinger render claims 6, 25, and 26 obvious. Ha additionally teaches articular cartilage, ear cartilage, nasal cartilage, elbow cartilage, meniscus, knee cartilage, costal cartilage, ankle cartilage, tracheal cartilage, laryngeal cartilage, and spinal cartilage (column 7, lines 40-45).
Regarding claim 29, the combined teachings of Ha, Pelekanos, and Edinger render claims 6 and 21 obvious. Additionally, Ha teaches treatment of cartilage damage, cartilage defect, bone defect, tendon-ligament defect, or fat tissue defect and further teaches that cartilage defect includes cartilage injury, cartilage tear, chondromalacia, cartilage necrosis, osteochondritis, cartilage loss, osteoarthritis (column 6, last para.; column 7, para. 1).
***
Claims 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Ha et al. (citation to US 10,232,000 B2, prior published US 2016/0324901 A1), in view of Pelekanos et al. (J Vis Exp. 2016 Jun 6:(112):54204. doi: 10.3791/54204., in view of Edinger et al. (US 2008/0152629 A1), and further in view of Ferreira et al. (Stem Cell Res Ther. 2018 Feb 5;9(1):28.; cited in Applicant’s PCT application and IDS).
The combined teachings of Ha, Pelekanos, and Edinger are applied as above in the 103, the content of which are incorporated herein rendering obvious the limitations of claims 6, 18, and 21-29.
Regarding claim 7, Ha in view of Pelekanos teaches the method of claim 6, as set forth above. Ferreira further teaches chorionic-villi-derived mesenchymal stromal cells lacking the cell-surface marker CD275 (pg. 9; column 1-2, bridging para.; Table 3).
Subject Matter Free of the Prior Art
A search directed to the specific surface-marker combination recited in claim 19 did not identify prior art disclosing a stem cell population having, in combination, (i) positive for CD44, CD73, CD90 and CD105; (ii) alternatively positive for CD49e, CD140b or CD142; (iii) negative for CD31, CD34, CD45 and HLA-DR; and iv) alternatively negative for CD273, CD275 or CD321, as recited in claim 19. Ha discloses CD44, CD73, CD90, and CD105 positivity together with CD31, CD34, CD45, and HLA-DR negativity, while Ferreira and the other references of record disclose certain additional individual markers. However, the search did not identify prior art teaching the specific combined marker expression profile recited in claim 19 in a single stem-cell population.
Response to Applicants' arguments as they apply to the rejection of Claims 6-7, 18, and 20-29 under 35 USC § 103
Applicants’ arguments filed December 23, 2025, have been fully considered but they are
not persuasive.
At pages 7-16 of the remarks filed on December 23, 2025, Applicants essentially argue
the following:
The crux of Applicants arguments is that Ha’s bCT is anatomically distinct from the claimed VCP region, that Ferreria concerns whole chorionic villi rather than the specifically defined VCP region, and that the VCP-derived cells exhibit unexpected properties, including fetal origin, increased colony formation and improved differentiation.
This argument is not persuasive because the present rejection does not rely upon Ha alone as disclosing the claimed VCP region. Instead, Ha teaches selecting a defined proximal portion of placental chorionic tissue, including approximately 20-30% and an exemplified 25% region, while Pelekanos teaches the specific anatomical dissecting of chorionic villi underlying the chorionic plate and obtaining stem cells. Thus, Pelekanos remedies the anatomical deficiency of Ha identified by Applicant. Regarding applicants arguments of improved properties, they are not commensurate in scope with the claims, as the claims do not require any particular colony-forming capacity or regenerative efficacy. Furthermore, the arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence, and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
Conclusion
Claims 6-7, 18, and 20-29 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOEL D LEVIN whose telephone number is (571)270-0616. The examiner be reached 8:00 am to 5:00 pm, Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher 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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/J.D.L./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
