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
Claim status
Claims 1-12 are pending
Claims 1-12 are under examination
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/21/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
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.
Claims 1-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al., (Int Wound J, 2017, 14:64-73), as evidenced by Hu et al. (Biomed Res Int, 2013, 438243), Min et al. (KR20190003303, filed 12/26/2017, published 11/13/2020, see IDS filed 6/21/2023), Pelagalli et al., (J Cell Phys, 2018, 233:6241-6249), Park et al. (In Vitro Cell Dev Bio, 2016, 52:68-76), and Sun et al., (Cell Transplant, 2019, 28:105-115)
With respect to claim 1, Li teaches the active step of improving skin condition by healing wounds comprising administering a composition comprising human umbilical cord-derived mesenchymal stem cell (UC-MSC) culture medium to a subject’s skin (p. 69, MSCs promote wound healing in vivo, see also Fig. 5).
In regard to claim 2, as stated supra, Li teaches the subject is in need of wound relief.
In regard to claim 11, directed to the markers of human UC-MSCs, although Li teaches that the UC-MSCs were measured with antibodies against CD44, CD90, and CD105, as well as CD14 and CD34 (p. 65, Isolation and culture of primary umbilical cord mesenchymal stem cells), they do not describe the results of the marker analysis. Nevertheless, Li cites the prior art of Hu et al. (2013) for the isolation and culturing of the UC-MSCs. Hu et al. evidences that the UC-MSCs are positive for CD44, CD90, and CD105, and negative for CD14 and CD34 (Section 3.2, Flow Cytometry).
In regard to claim 12, Li teaches the active steps for preparing the UC-MSC-CM comprising: a) isolating MSCs from human umbilical cord from which blood vessels (both arteries and veins) were removed,
b) subculturing the MSCs in serum-free DMEM,
c) ultrafiltration of the condition media obtained (p. 65, Preparation of conditioned medium).
In regard to the wherein clauses of Claims 3-10, it is noted that these wherein clauses do not recite any additional active method steps nor are they directed to a particular patient population or structurally distinct UC-MSC cell type, but simply state a characterization or conclusion of the results of process step positively recited (e.g. administering the prepared composition from UC-MSCs). Therefore, these "wherein" clauses are not considered to further limit the method/patient/cells defined by claims 1-2 and 11-12. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."). See also MPEP 2111.04 that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.”
Furthermore, the Examiner has provided the following extrinsic evidence to make clear that the missing descriptive matter is necessarily present in the UC-MSC derived conditioned media described in the reference of Li, and that it would have been recognized by persons of ordinary skill at the time of filing:
In regard to Claims 3-5 directed to the factors secreted by human UC-MSCs into conditioned media, although Li teaches that MSCs promote wound repair by the secretion of soluble factors (p. 65, 1st para.), they do not describe the factors in the media.
Min et al. prepare human UC-MSCs from human umbilical cord from which blood vessels are removed, and cultured, and the secreted factors were measured [0067], p. 38 of English translation). Specifically, Min evidences that undifferentiated UC-MSCs secrete IGFBP-rp1/IGFBP-7, ANGPTL-1, ANGPTL-2, thrombospondin-1, TIMP-2, EDA-A2, GDF-15, GRO, TIMP-1 and CCR4 (Table 2, [0090], Fig. 5, see pgs. 48-50 of English translation). Thus, Min et al. evidence that a culture media derived from human UC-MSCs would inherently have the claimed factors.
In regard to claim 6, Li demonstrates the composition promotes collagen III synthesis in skin fibroblasts (Fig. 2B).
In regard to Claim 7, directed to aquaporin synthesis promoting effects of UC-MSC conditioned media, although Li teaches that the UC-MSC culture media enhances cell migration into the wound bed (Abstract, Fig.1), they do not describe the enhanced migratory effects as being due to increased aquaporin production.
Pelagalli et al. describe the effects of conditioned media from MSCs on cell migration during wound healing (Abstract, p. 6243, Results, Section 3.1, see also Fig. 1). Pelagalli discloses the enhanced effects on cell migration are due to increased aquaporin-1 expression in the migrating cells. Thus, Pelagalli evidence that a culture media derived from MSCs would inherently have the claimed effects on aquaporin expression, and one of ordinary skill would have understood that these effects would reasonably extend to conditioned media from UC-MSCs.
In regard to Claim 8, directed to the anti-inflammatory effects of UC-MSC conditioned media, although Li teaches that the UC-MSC culture media enhances skin scarless repair, which is associated with reduced inflammation (Introduction, Fig. 5, legend), they do not describe the anti-inflammatory effects on ROS production in the skin.
Park et al. describe a method of improving tissue condition by preventing muscle atrophy comprising administering a composition comprising conditioned culture media from human UC-MSCs prepared from a human umbilical cord tissue from which blood vessels are removed (p. 69, Umbilical cord mesenchymal stem cell preparation). Park discloses the composition inhibits the production of ROS in muscle cells (p. 73, Fig. 4). Thus, Park et al. evidence that a culture media derived from human UC-MSCs would inherently have the claimed effects on ROS, and one of ordinary skill would have understood that these effects would reasonably extend to muscle cells of the skin.
In regard to Claims 9-10, directed to the anti-inflammatory effects of UC-MSC conditioned media, although Li teaches that the UC-MSC culture media enhances skin scarless repair, which is associated with reduced inflammation (Introduction, Fig. 5, legend), they do not describe the anti-inflammatory effects on cytokines in the skin.
Sun et al. describe a method of improving skin condition by healing wounds comprising administering a composition comprising UC-MSC derived culture medium to a subject’s skin (p. 106, Conditioned Medium Preparation, p. 107, Animals and treatments, see also Fig. 3). Sun discloses the composition inhibits the production of inflammatory cytokines such as TNF-alpha in human endothelial cells (p. 108, Fig. 2d). Thus, Sun et al. evidence that a culture media derived from UC-MSCs would inherently have the claimed effects on inflammatory cytokines such as TNF-alpha, and one of ordinary skill would have understood that these effects would reasonably extend to endothelial cells of the skin.
In conclusion with regard to the wherein clauses of Claims 3-10, since the Patent Office does not have the facilities for examining and comparing Applicants' UC-MSC derived culture media with the UC-MSC derived culture media from the prior art reference of Li et al., the burden is upon Applicants to show a distinction between the material structural and functional characteristics of the claimed culture media and the culture media of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Accordingly, Li, as evidenced by Hu, Min, Pelagalli, Park and Sun, anticipates instant claims.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/ Examiner, Art Unit 1631