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 .
Amendments
In the reply filed 4/14/2026, Applicant has amended Claims 1 and 12, and cancelled claims 2-10.
Claims 1, and 11-12 under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/14/2026 was filed after the mailing date of the non-final Office action on 1/14/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
New Objection to Specification
The use of the term RayBio, which is a trade name or a mark used in commerce, has been noted in this application. The term should 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.
Withdrawn 35 USC § 102
The prior rejection of Claims 1, 11-12 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 (In Vitro Cell Dev Bio, 2016, 52:68-76), and Sun et al., (Cell Transplant, 2019, 28:105-115) is withdrawn in light of Applicant’s amendment of Claim 1 to limit the skin condition to improved barrier strength by increasing AQP3, HAS-2 and/or HAS-3, and to limit the conditioned media to comprise 6Ckine, adiponectin/Acrp30, angiogenin, ANGPT-1, ANGPT-2, ANGPTL-1, ANGPTL-2, angiostatin, APRIL, artemin, BD-1, BAX, BMP-2, BMP-3, BMP-4, BMPR-IA/ALK-3, CCR1, CCR2, CCR4, CCR6, CCR7, CCR8, CCR9, CD30 ligand/TNFSF8, CD40/TNFRSF5, CD40 ligand/TNFSF6/CD154, Csk, CLC, CRTH-2, CTACK/CCL27, CXCR1/IL-8 RA, CXCR2/IL-8 RB, CXCR5/BLR-1, EDA-A2, EDG-1, EG-VEGF/PK1, endostatin, ErbB4, Fas ligand, FGF Basic, FGF R4, FGF-9, FGF-10/KGF-2, FGF-11, IL-13 1B, GDF3, GDF5, GDF9, GDF11, GDF-15, GRO-a, HB-EGF, HCR(CRAM-A/B), HRG1-α/NRG1-a. IGFBP-3, IGFBP-6, IGFBP- rp1/IGFBP-7, lymphotoxin-B/TNFSF3, M-CSF, MDC, MIP-1a, MIP-1b, MIP 2, NAP-2, PF4/CXCL4, PLUNC, thrombospondin-1, TIMP-1, TIMP-2, TMEFF1/tomoregulin-1, and TRADD.
Specifically, Applicant argues that the claimed method directed to improving skin barrier strength requires a distinct biological mechanism from the wound healing and reduced scarring as taught by Li. Moreover, Applicant argues that there is a concentration-dependent increase of AQP3, HAS-2, and HAS-3 in cultured human epidermal cells when using the claimed UC-MSC culture medium, which represent an effect unique to the claimed culture media and could not have been predicted from the prior art.
Furthermore, Applicant argues that the claimed conditioned culture media structurally distinct from the cited prior art. Specifically, Applicant argues that the closest prior art of Min teaches a conditioned culture media where only 10 proteins are found among the 71 proteins claimed. Moreover, among these remaining 61 proteins, including FGF-9, CCR7, MIP-1a, APRIL, and angiostatin, are key highly-expressed proteins in the claimed conditioned culture media. Applicant argues that “the composition ratio of proteins, rather than the mere presence or absence of individual proteins, that determines the biological activity of a culture media, and such differences in compositional ratio constitute an essential distinction between the present invention and the cited reference.” Therefore, Applicant argues that even if some proteins are partially shared between conditioned media, “a completely different cellular response may be induced when the expression levels and composition ratios of the key factor differ, which means that the efficacy of a culture medium is determined not merely by a list of its constituents components but by their quantitative balance.”
New Claim Rejections - 35 USC § 112(b)
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 1, 11 and 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01.
In regard to claim 1, instant claim fails to include essential elements of the invention as defined by Applicant in the remarks filed 4/14/2026. Note MPEP 2172.01 states that such essential matter may include missing elements, steps or necessary structural cooperative relationships of elements described by the Applicant(s) as necessary to practice the invention. In instant method of improving skin barrier function by increasing AQP3, HAS-2, and/or HAS-3, by administering to a subject a conditioned culture media from umbilical cord-derived mesenchymal stem cells fails to recite the composition ratio of the 71 proteins claimed in the conditioned media. Absent claim language indicating the composition ratio of the 71 proteins claimed, a person of ordinary skill in the art could not interpret the metes and bounds of the claim because a completely different cellular response may be induced when the expression levels and composition ratios of the key factor differ, which means that the efficacy of a culture medium is determined not merely by a list of its constituents components but by their quantitative balance. In other words, conditioned media is a complex undefined mixture of proteins that depend on the specific cell type, culture conditions, and processing steps, all of which contribute “to differences in compositional ratio (that) constitute an essential distinction” between Applicant’s invention and the prior art.
Dependent claims 11 and 12 are included in the basis of the rejection because although it recites and encompasses the method of claim 1, they do not clarify the composition ratio of the claimed 71 proteins in the conditioned media.
New Claim Rejections - 35 USC § 112(a)
(Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 11-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 encompasses methods of improving a skin condition comprising administering to a subject’s skin and umbilical cord-derived mesenchymal stem cell (UC-MSC) culture media as the active ingredient, wherein the improvement in the skin condition comprises a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3, wherein the umbilical cord-derived mesenchymal stem cell culture media comprises 6Ckine, adiponectin/Acrp30, angiogenin, ANGPT-1, ANGPT-2, ANGPTL-1, ANGPTL-2, angiostatin, APRIL, artemin, BD-1, BAX, BMP-2, BMP-3, BMP-4, BMPR-IA/ALK-3, CCR1, CCR2, CCR4, CCR6, CCR7, CCR8, CCR9, CD30 ligand/TNFSF8, CD40/TNFRSF5, CD40 ligand/TNFSF6/CD154, Csk, CLC, CRTH-2, CTACK/CCL27, CXCR1/IL-8 RA, CXCR2/IL-8 RB, CXCR5/BLR-1, EDA-A2, EDG-1, EG-VEGF/PK1, endostatin, ErbB4, Fas ligand, FGF Basic, FGF R4, FGF-9, FGF-10/KGF-2, FGF-11, IL-13 1B, GDF3, GDF5, GDF9, GDF11, GDF-15, GRO-a, HB-EGF, HCR(CRAM-A/B), HRG1-α/NRG1-a. IGFBP-3, IGFBP-6, IGFBP- rp1/IGFBP-7, lymphotoxin-B/TNFSF3, M-CSF, MDC, MIP-1a, MIP-1b, MIP 2, NAP-2, PF4/CXCL4, PLUNC, thrombospondin-1, TIMP-1, TIMP-2, TMEFF1/tomoregulin-1, and TRADD.
In regard to the scope of the skin conditions related to improving barrier function to be treated, Applicant’s specification describes the improved barrier function by various moisturizing factors such as hyaluronic acid, which is mainly synthesized by HAS of keratinocytes and fibroblasts and accumulate in the extracellular matrix (Example 6, p. 34, 2nd para.), and that skin moisturizing or a barrier strengthening effect is promoted aquaporin or hyaluronic acid synthesis (p. 9, 1st three para.).
In regard to the scope of the umbilical cord-derived mesenchymal stem cells (MSC), Applicant’s specification describes the “umbilical cord-derived mesenchymal stem cells” may refer to cells derived from umbilical cord or Wharton’s jelly tissue, but also includes sources of the cells as from umbilical cord blood (p. 3, 2nd & 3rd para).
In regard to the scope of the conditioned media, Applicant discloses a genus of conditioned media that are obtained by subculturing umbilical cord-derived mesenchymal stem cells 1 to 10 times in serum-free cell culture medium, and filtering the culture medium obtained in the subculturing steps (p. 10, 4th para., p. 11, 4th and 5th para.).
Dependent claim 11 encompasses a genus of methods comprising a genus umbilical cord-derived mesenchymal stem cells that are positive for CD44, CD73, CD105, and/or CD90, and are negative for CD14, CD19, CD45, and/or CD34.
Dependent claim 12 encompasses a genus of methods for preparing the culture media comprising a) isolating mesenchymal stem cells from umbilical cord from which blood vessels are removed; b) subculturing the isolated mesenchymal stem cells 1 to 10 times in serum-free cell culture medium; and c) filtering after culture medium is obtained in the subculturing step.
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). Written description issues may also arise if the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed product arising from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996).
Accordingly, instant specification fails to satisfy the written description requirement because the claimed invention is not described in sufficient detail such that one skilled in the art could make and use the claimed UC-MSC conditioned culture media to improve a skin condition.
ACTUAL REDUCTION TO PRACTICE
In regard to claim 1 encompassing a genus of methods for improving skin conditions comprising administering to a subject’s skin and umbilical cord-derived mesenchymal stem cell culture media as the active ingredient, wherein the improvement in the skin condition comprises a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3, the specification provides no methods of treating any skin condition in a subject, and only describes in vitro experiments with human epidermal cells (HaCaT) and human dermal fibroblasts (HS68), with a single type of conditioned culture media from a single type of umbilical derived cell (Example 6, pgs. 32-34).
In regard to the scope of the genus of umbilical cord-derived mesenchymal stem cells, Applicant’s specification describes a specific type of umbilical cord-derived mesenchymal stem cell prepared by the process steps of obtaining a human umbilical cord provided during delivery of a healthy mother, washing the human umbilical cord washed with phosphate buffered saline (PBS) in a cell culture dish on ice, removing the blood vessels in the human umbilical cord were with sterilized scissors, followed by finely cutting to a size of about 3 mm to about 5 mm. The finely cut umbilical cord tissues were transferred to a cell culture flask, followed by treatment with a trypsin enzyme to allow a reaction to occur at 37 °C for 30 minutes, and MEM-alpha medium containing 5% human platelet lysate (HPL), 1% penicillin/streptomycin (P/S) was added thereto and the tissues were cultured in an incubator at 37 °C, to thereby obtain umbilical cord-derived mesenchymal stem cells (Example 1, pgs. 19-20).
Importantly, in regard to the scope of the conditioned culture media, Applicant discloses the obtained mesenchymal stem cells were subcultured three times or four times, and then, when the confluency of the cells reached 70% to 80%, the culture medium was replaced with phenol-red free MEM-alpha containing 5% human platelet lysate (HPL) and 1 % P/S, followed by culturing for 48 hours, to separate a culture medium. The separated culture medium was filtered with a 0.22 μm filter to obtain an umbilical cord-derived mesenchymal stem cell culture medium.
Moreover, in regard to the scope of the proteins in the conditioned media, Applicant discloses that the secretome of the umbilical cord-derived mesenchymal stem cell culture medium obtained in the preparation Example 1 was analyzed with a RayBio Human Cytokine/Growth Factor Antibody (RayBiotech, Noncross, GA, USA) to assess the components of the umbilical cord-derived mesenchymal stem cell culture medium in a serum-free state (Example 2, p. 24). This analysis of the 71 proteins present and their relative composition ratio was determined from a single media sample as presented in Table 3 of Applicant’s specification, yet it did not account for any batch-to-batch variation in the media preparation process, and did not compare the secretome results to a control sample media that was not exposed to cells.
In regard to dependent claim 11 encompassing a genus of methods comprising a genus umbilical cord-derived mesenchymal stem cells that are positive for CD44, CD73, CD105, and/or CD90, and are negative for CD14, CD19, CD45, and/or CD34, Applicant’s specification discloses a single type of umbilical cord-derived mesenchymal stem cell that positive for CD44, CD73, CD105, and CD90, and are also negative for CD14, CD19, CD45, and CD34 (Examples 1.3, pgs. 22-24).
In regard to dependent claim 12 encompassing a genus of methods a genus of methods for preparing the culture media comprising a) isolating mesenchymal stem cells from umbilical cord from which blood vessels are removed; b) subculturing the isolated mesenchymal stem cells 1 to 10 times in serum-free cell culture medium; and c) filtering after culture medium is obtained in the subculturing step, as stated supra, the specification describes only subculturing three times or four times, and then, when the confluency of the cells reached 70% to 80%, the culture medium was replaced with phenol-red free MEM-alpha containing 5% human platelet lysate (HPL) and 1 % P/S, followed by culturing for 48 hours, to separate a culture medium. Which was filtered with a 0.22 μm filter.
Accordingly, Applicant did not demonstrate a reduction to practice of a method of improving a skin condition in a subject, with any type of umbilical cord-derived stem cell, using a culture media made and characterized by any means, nor did Applicant adequately set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of methods, particularly with respect to permitting the ordinary artisan to make and use the claimed conditioned cell culture product arising from the disclosed process.
DISCLOSURE OF STRUCTURE
The Applicant has provided no examples of a method of treating a skin condition in a subject comprising a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3, comprising administering an umbilical cord-derived mesenchymal stem cell culture media as the active ingredient, wherein the culture media comprises 6Ckine, adiponectin/Acrp30, angiogenin, ANGPT-1, ANGPT-2, ANGPTL-1, ANGPTL-2, angiostatin, APRIL, artemin, BD-1, BAX, BMP-2, BMP-3, BMP-4, BMPR-IA/ALK-3, CCR1, CCR2, CCR4, CCR6, CCR7, CCR8, CCR9, CD30 ligand/TNFSF8, CD40/TNFRSF5, CD40 ligand/TNFSF6/CD154, Csk, CLC, CRTH-2, CTACK/CCL27, CXCR1/IL-8 RA, CXCR2/IL-8 RB, CXCR5/BLR-1, EDA-A2, EDG-1, EG-VEGF/PK1, endostatin, ErbB4, Fas ligand, FGF Basic, FGF R4, FGF-9, FGF-10/KGF-2, FGF-11, IL-13 1B, GDF3, GDF5, GDF9, GDF11, GDF-15, GRO-a, HB-EGF, HCR(CRAM-A/B), HRG1-α/NRG1-a. IGFBP-3, IGFBP-6, IGFBP- rp1/IGFBP-7, lymphotoxin-B/TNFSF3, M-CSF, MDC, MIP-1a, MIP-1b, MIP 2, NAP-2, PF4/CXCL4, PLUNC, thrombospondin-1, TIMP-1, TIMP-2, TMEFF1/tomoregulin-1, and TRADD.
Importantly, Applicant has not sufficiently disclosed the process for making and using claimed UC-MSC conditioned culture media with respect to the precise cell type, number of cells, starting materials, culture conditions, composition ratios of the 71 proteins, and means for detecting these proteins so as to arrive at the conditioned media comprising the composition ratios of Table 3.
Furthermore, the prior art indicates that conditioned media are complex mixture of proteins and is silent with respect to methods of making and using the claim condition culture media comprising the indicated 71 proteins at composition ratios for improving skin conditions in a subject. Furthermore, neither the specification nor the art indicate a relationship between the structure of the claimed culture media and the ability to successfully treat a skin condition in a subject with respect to the composition ratios of the 71 proteins, and the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed conditioned culture product arising from the disclosed process.
SUFFICIENT RELEVANT IDENTIFYING CHARACTERISTICS
Methods for improving skin conditions comprising the administration of UC-MSC conditioned culture media were known, and the proteins claimed to be in conditioned culture media were known in the prior art. Furthermore, it was known that umbilical cord-derived mesenchymal stem cells are positive for CD44, CD73, CD105, and CD90, and are also negative for CD14, CD19, CD45, and CD34.
However, the breadth of the claims encompass the making and using of an active ingredient that is derived from genus of umbilical cord-derived mesenchymal stem cell types by a genus of methods for making the conditioned culture media comprising the claimed 71 proteins at the proper composition ratio to achieve the effect of improving a skin condition by strengthening barrier function by increasing AQP2, HAS-2, and/or HAS-3.
The claimed condition culture media comprising the claimed 71 proteins at composition ratios sufficient to improve skin barrier function by increasing AQP2, HAS-2, and/or HAS-3 is not taught by the prior art, and the present specification provides limited guidance and description of methods of making and using the claimed composition, and describes a single technique using a proprietary RayBio kit to establish the composition ratios of a single culture media sample, therefore the skilled artisan would not know what rational approach to take to make and use the claimed composition comprising the 71 proteins at the proper composition ratio to predictably function in improving the skin condition in a subject as claimed. Therefore, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of the claimed genus of methods.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of practicing the claimed invention is not well established. Although methods for improving skin conditions comprising the administration of UC-MSC conditioned culture media were known, and the proteins claimed to be in conditioned culture media were known in the prior art, one of skill in the art would neither expect nor predict a successful outcome for a method of improving a skin condition in a subject comprising a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3, comprising administering an umbilical cord-derived mesenchymal stem cell culture media as the active ingredient as claimed.
The following describes the state of the art with respect to methods for making and using a UC-MSC conditioned culture media to improve skin conditions.
Firstly, Kim et al. (Biochem Biophys Rep, 2018, 96-102, see IDS filed 4/14/2026) teach a method of improving skin condition comprising applying an umbilical cord-derived mesenchymal stem cell culture media in vitro to dermal fibroblasts to stimulate growth and extracellular matrix production, and in vivo to reduce wrinkles and increase dermal density (Abstract). Importantly, using the RayBiotech array similar or identical to Applicant’s, Kim (2018) analyzed the presence of an array of proteins secreted in umbilical cord-derived mesenchymal stem cell culture media and did not find the 71 protein as claimed (see Fig. 1A). Thus, Kim (2018) established that despite making a UC-MSC conditioned culture media and using the same or similar techniques described in Applicant’s specification to characterize said media, the ordinary artisan could not predictably arrive at the claimed cell culture media product arising from the disclosed process.
Furthermore, Kim (2018) teaches that the expression level of the proteins detected by said array are significantly affected by the media used and the time the UC-MSCs are in culture. Specifically, Kim (2018) demonstrates that a culture media supplemented with as little as 10ng/ml EGF shows up on the array at time 0 hr (see Fig. 1B). Thus, Kim (2018) established that the starting materials used for making UC-MSC conditioned media are critical for establishing the final presence and composition ratios of the proteins in the conditioned media. Note that as stated supra, Applicant’s uses a distinct primary UC-MSC cell type isolated and subcultured by a specific method at a specific range of confluence (70-80%) with a specific starting media of MEM-alpha and 5% human platelet lysate.
Moreover, in regard to the effects of 5% human platelet lysate (HPL) on the composition ratio of a UC-MSC conditioned culture media, as a first matter, it well known HPL is a complex mixture of numerous cytokines and growth factors that would contribute to the composition ratio of the final conditioned culture media. Furthermore, Weiss et al. (WO2017/132358) teaches and claims methods of producing UC-MSCs and has demonstrated 5% HPL significantly effects UC-MSC cell proliferation by orders of magnitude as well as cell viability (pgs. 16-17, MSC Expansion Comparison, see Fig. 3), which would also be expected to effect the final conditioned culture media.
Second, Kim (2018) demonstrates that the measured composition ratios of the proteins in the UC-MSC conditions media change over time in culture. Specifically, Kim shows that as little as a 12 hour difference in culture time can have a significant impact on the composition ratio of a protein in the conditioned media (see Fig. 1B). Thus, Kim (2018) established that that the composition ratios of the proteins in the UC-MSC conditions media are highly dependent on the time in culture. Note that as stated supra, Applicant’s uses a distinct UC-MSC with a specific starting media for 48 hours.
Third, as far as culture conditions influencing the making and using UC-MSC conditioned culture media, Miranda et al. (Frontiers Immuno, 2019 10:1-14) teaches that secretome profile and therapeutic potential of the condition media changed depending on the culture conditions. Similar to Kim, Miranda makes a conditioned media from UC-MSCs, but Miranda teach the resulting media only comprises one (FGF-2) of the 71 proteins as claimed. Specifically, Miranda cultured UC-MSC on a 2D monolayer versus a 3D spinner-flask after 48 hours of conditioning, wherein the spinner-flask conditioned media was characterized by a prevailing expression of anti-inflammatory cytokines such as IL-10 and LIF, along with trophic factors involved in different mechanisms leading to tissue regeneration, such as PDGF-BB, FGF-2, I-309, SCF, and GM-CSF, while the static 2D monolayer derived conditioned media contained relatively higher levels of pro-inflammatory cytokines IL-6, MCP-1, and IL-21 (Abstract, p. 6. Fig. 2). Thus, Miranda established that that the composition ratios of the proteins in the UC-MSC conditions media are highly dependent on the static or dynamic culture conditions. Note that as stated supra, Applicant’s uses a distinct UC-MSC with a specific starting media for specific time, but does not describe the culture conditions with sufficient detail to permit the ordinary artisan to immediately envisage the claimed culture media product arising from the disclosed process.
Fourth, the prior art of Shen et al (Mol Med Rep, 2015, 12:20-30) teaches a method of treating a skin condition comprising administering a composition comprising human umbilical cord-derived mesenchymal stem cell (UC-MSC) culture medium to a subject’s skin (Abstract). Furthermore, Shen teaches the active steps for preparing the UC-MSC-CM comprising: a) isolating MSCs from human umbilical cord from Wharton’s jelly (which does not include the arteries and veins), b) culturing the UC-MSCs in serum-free DMEM for 72 hours, c) ultrafiltration of the condition media through a 0.22 micron filter (p. 21, Materials and Methods). However, when Shen examines presence of cytokines and growth factors present in the conditioned media, only one protein (FGF-2) is shared with the 71 proteins claimed (Table 1). Thus, Shen establishes that that the composition ratios of the proteins in the UC-MSC conditions media are highly variable and depend on the UC-MSC isolation conditions and the methods of detection. Note that as stated supra, Applicant’s uses a distinct UC-MSC with a specific starting media for specific time, with specific procedures for isolating and subculturing the UC-MSC, but relies on a single proprietary commercial kit from RayBio for detecting the 71 cytokines and their composition ratios from a single conditioned culture media sample with no accounting for batch to batch variations, nor control media that had not been exposed to cells. Again, instant specification does not describe the detection methods with sufficient detail to permit the ordinary artisan to immediately envisage the claimed culture media product arising from the disclosed process.
Fifth, the post filing review of Li et al. (Cell Proliferation, 2024;57:1-16) evidences that the UC-MSC secretome found in conditioned media is a complex mixture of proteins released by a variety of ways including exosomes, microvesicles, and apoptotic bodies (see Fig. 1), and the nature of the secretome is influenced by the UC-MSC source, culture conditions, separation method, identification technique, storage, and pretreatment of cells (Abstract, pgs. 9-11, Section 4, see Table 1). This post filing evidence, coupled with Applicant’s admission that “the composition ratio of proteins, rather than the mere presence or absence of individual proteins, that determines the biological activity of a culture media, and … a completely different cellular response may be induced when the expression levels and composition ratios of the key factor differ, which means that the efficacy of a culture medium is determined not merely by a list of its constituents components but by their quantitative balance” evidence that the instant specification has not sufficiently described how to make the active ingredient of the claimed invention.
Applicant has claimed a genus of methods to improve skin conditions in a subject that strengthen barrier function by increasing expression of AQP3, HAS-2, and/or HAS-3 comprising administering a UC-MSC conditioned culture comprising a distinct combination of 71 different cytokines and growth factors, yet the specification has not disclosed such methods in a subject, has not set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of methods, and has not provided sufficient detail to permit the ordinary artisan to immediately envisage the claimed culture media product arising from the disclosed process. Furthermore, the state of the art indicated that practicing the claimed method is not well established with the claimed function in successfully improving skin conditions in a subject with the claimed UC-MSC conditioned culture media would require undue experimentation.
CONCLUSION
Therefore, the Examiner concludes that there is insufficient written description of the instantly claimed genus methods for improving a skin condition in a subject comprising administering an effective amount of the UC-MSC culture media, wherein the UC-MSC culture media comprise a genus of 71 distinct proteins at a distinct composition ratio. Specifically, there is limited description of the structure-function relationship between the claimed genus culture media comprising the composition ratios of the 71 proteins present and their ability to improve a skin condition by strengthening barrier function, and the Examiner further concludes a skilled artisan would find the specification inadequately describes the claimed genus of methods, and has not provided sufficient detail to permit the ordinary artisan to immediately envisage the claimed culture media product arising from the disclosed process.
New Claim Rejections - 35 USC § 112(a)
(Scope of Enablement)
Claims 1, 11 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of improving a skin condition in a subject comprising administering to a subject’s skin an umbilical cord-derived mesenchymal stem cell (UC-MSC) culture media as the active ingredient,
wherein the improvement in the skin condition comprises a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3,
wherein the umbilical cord-derived mesenchymal stem cell culture media comprises 6Ckine, adiponectin/Acrp30, angiogenin, ANGPT-1, ANGPT-2, ANGPTL-1, ANGPTL-2, angiostatin, APRIL, artemin, BD-1, BAX, BMP-2, BMP-3, BMP-4, BMPR-IA/ALK-3, CCR1, CCR2, CCR4, CCR6, CCR7, CCR8, CCR9, CD30 ligand/TNFSF8, CD40/TNFRSF5, CD40 ligand/TNFSF6/CD154, Csk, CLC, CRTH-2, CTACK/CCL27, CXCR1/IL-8 RA, CXCR2/IL-8 RB, CXCR5/BLR-1, EDA-A2, EDG-1, EG-VEGF/PK1, endostatin, ErbB4, Fas ligand, FGF Basic, FGF R4, FGF-9, FGF-10/KGF-2, FGF-11, IL-13 1B, GDF3, GDF5, GDF9, GDF11, GDF-15, GRO-a, HB-EGF, HCR(CRAM-A/B), HRG1-α/NRG1-a. IGFBP-3, IGFBP-6, IGFBP- rp1/IGFBP-7, lymphotoxin-B/TNFSF3, M-CSF, MDC, MIP-1a, MIP-1b, MIP 2, NAP-2, PF4/CXCL4, PLUNC, thrombospondin-1, TIMP-1, TIMP-2, TMEFF1/tomoregulin-1, and TRADD,
wherein the UC-MSC are positive for CD44, CD73, CD105, and CD90, and are also negative for CD14, CD19, CD45, and CD34,
wherein the UC-MSCs are obtained by a process from a human umbilical cord provided during delivery of a healthy mother, washing the human umbilical cord washed with phosphate buffered saline (PBS) in a cell culture dish on ice, removing the blood vessels in the human umbilical cord were with sterilized scissors, followed by finely cutting to a size of about 3 mm to about 5 mm. The finely cut umbilical cord tissues were transferred to a cell culture flask, followed by treatment with a trypsin enzyme to allow a reaction to occur at 37 °C for 30 minutes, and MEM-alpha medium containing 5% human platelet lysate (HPL), 1% penicillin/streptomycin (P/S) was added thereto and the tissues were cultured in an incubator at 37 °C,
wherein the conditioned media is obtained from the UC-MSC having been subcultured three times or four times, and then, when the confluency of the cells reached 70% to 80%, the culture medium was replaced with phenol-red free MEM-alpha containing 5% human platelet lysate (HPL) and 1 % P/S, followed by culturing for 48 hours, to separate a culture medium. The separated culture medium was filtered with a 0.22 μm filter to obtain an umbilical cord-derived mesenchymal stem cell culture medium,
wherein the conditioned media has been analyzed with a RayBio Human Cytokine/Growth Factor Antibody (RayBiotech, Noncross, GA, USA) to establish that the culture media comprises the composition ratio of Table 3 of Applicant’s specification,
does not reasonably provide enablement for methods of improving skin condition with any UC-MSC conditioned culture media as the active ingredient. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
SCOPE OF THE INVENTION
Independent claim 1 encompasses methods of improving a skin condition comprising administering to a subject’s skin and umbilical cord-derived mesenchymal stem cell (UC-MSC) culture media as the active ingredient, wherein the improvement in the skin condition comprises a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3, wherein the umbilical cord-derived mesenchymal stem cell culture media comprises 6Ckine, adiponectin/Acrp30, angiogenin, ANGPT-1, ANGPT-2, ANGPTL-1, ANGPTL-2, angiostatin, APRIL, artemin, BD-1, BAX, BMP-2, BMP-3, BMP-4, BMPR-IA/ALK-3, CCR1, CCR2, CCR4, CCR6, CCR7, CCR8, CCR9, CD30 ligand/TNFSF8, CD40/TNFRSF5, CD40 ligand/TNFSF6/CD154, Csk, CLC, CRTH-2, CTACK/CCL27, CXCR1/IL-8 RA, CXCR2/IL-8 RB, CXCR5/BLR-1, EDA-A2, EDG-1, EG-VEGF/PK1, endostatin, ErbB4, Fas ligand, FGF Basic, FGF R4, FGF-9, FGF-10/KGF-2, FGF-11, IL-13 1B, GDF3, GDF5, GDF9, GDF11, GDF-15, GRO-a, HB-EGF, HCR(CRAM-A/B), HRG1-α/NRG1-a. IGFBP-3, IGFBP-6, IGFBP- rp1/IGFBP-7, lymphotoxin-B/TNFSF3, M-CSF, MDC, MIP-1a, MIP-1b, MIP 2, NAP-2, PF4/CXCL4, PLUNC, thrombospondin-1, TIMP-1, TIMP-2, TMEFF1/tomoregulin-1, and TRADD.
In regard to the scope of the skin conditions related to improving barrier function to be treated, Applicant’s specification describes the improved barrier function by various moisturizing factors such as hyaluronic acid, which is mainly synthesized by HAS of keratinocytes and fibroblasts and accumulate in the extracellular matrix (Example 6, p. 34, 2nd para.), and that skin moisturizing or a barrier strengthening effect is promoted aquaporin or hyaluronic acid synthesis (p. 9, 1st three para.).
In regard to the scope of the umbilical cord-derived mesenchymal stem cells (MSC), Applicant’s specification describes the “umbilical cord-derived mesenchymal stem cells” may refer to cells derived from umbilical cord or Wharton’s jelly tissue, but also includes sources of the cells as from umbilical cord blood (p. 3, 2nd & 3rd para).
In regard to the scope of the conditioned media, Applicant discloses a genus of conditioned media that are obtained by subculturing umbilical cord-derived mesenchymal stem cells 1 to 10 times in serum-free cell culture medium, and filtering the culture medium obtained in the subculturing steps (p. 10, 4th para., p. 11, 4th and 5th para.).
Dependent claim 11 encompasses a genus of methods comprising a genus umbilical cord-derived mesenchymal stem cells that are positive for CD44, CD73, CD105, and/or CD90, and are negative for CD14, CD19, CD45, and/or CD34.
Dependent claim 12 encompasses a genus of methods for preparing the culture media comprising a) isolating mesenchymal stem cells from umbilical cord from which blood vessels are removed; b) subculturing the isolated mesenchymal stem cells 1 to 10 times in serum-free cell culture medium; and c) filtering after culture medium is obtained in the subculturing step.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention.
ACTUAL REDUCTION TO PRACTICE
In regard to claim 1 encompassing a genus of methods for improving skin conditions comprising administering to a subject’s skin and umbilical cord-derived mesenchymal stem cell culture media as the active ingredient, wherein the improvement in the skin condition comprises a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3, the specification provides no methods of treating any skin condition in a subject, and only describes in vitro experiments with human epidermal cells (HaCaT) and human dermal fibroblasts (HS68), with a single type of conditioned culture media from a single type of umbilical derived cell (Example 6, pgs. 32-34).
In regard to the scope of the genus of umbilical cord-derived mesenchymal stem cells, Applicant’s specification describes a specific type of umbilical cord-derived mesenchymal stem cell prepared by the process steps of obtaining a human umbilical cord provided during delivery of a healthy mother, washing the human umbilical cord washed with phosphate buffered saline (PBS) in a cell culture dish on ice, removing the blood vessels in the human umbilical cord were with sterilized scissors, followed by finely cutting to a size of about 3 mm to about 5 mm. The finely cut umbilical cord tissues were transferred to a cell culture flask, followed by treatment with a trypsin enzyme to allow a reaction to occur at 37 °C for 30 minutes, and MEM-alpha medium containing 5% human platelet lysate (HPL), 1% penicillin/streptomycin (P/S) was added thereto and the tissues were cultured in an incubator at 37 °C, to thereby obtain umbilical cord-derived mesenchymal stem cells (Example 1, pgs. 19-20).
Importantly, in regard to the scope of the conditioned culture media, Applicant discloses the obtained mesenchymal stem cells were subcultured three times or four times, and then, when the confluency of the cells reached 70% to 80%, the culture medium was replaced with phenol-red free MEM-alpha containing 5% human platelet lysate (HPL) and 1 % P/S, followed by culturing for 48 hours, to separate a culture medium. The separated culture medium was filtered with a 0.22 μm filter to obtain an umbilical cord-derived mesenchymal stem cell culture medium.
Moreover, in regard to the scope of the proteins in the conditioned media, Applicant discloses that the secretome of the umbilical cord-derived mesenchymal stem cell culture medium obtained in the preparation Example 1 was analyzed with a RayBio Human Cytokine/Growth Factor Antibody (RayBiotech, Noncross, GA, USA) to assess the components of the umbilical cord-derived mesenchymal stem cell culture medium in a serum-free state (Example 2, p. 24). This analysis of the 71 proteins present and their relative composition ratio was determined from a single media sample as presented in Table 3 of Applicant’s specification, yet it did not account for any batch-to-batch variation in the media preparation process, and did not compare the secretome results to a control sample media that was not exposed to cells.
In regard to dependent claim 11 encompassing a genus of methods comprising a genus umbilical cord-derived mesenchymal stem cells that are positive for CD44, CD73, CD105, and/or CD90, and are negative for CD14, CD19, CD45, and/or CD34, Applicant’s specification discloses a single type of umbilical cord-derived mesenchymal stem cell that positive for CD44, CD73, CD105, and CD90, and are also negative for CD14, CD19, CD45, and CD34 (Examples 1.3, pgs. 22-24).
In regard to dependent claim 12 encompassing a genus of methods a genus of methods for preparing the culture media comprising a) isolating mesenchymal stem cells from umbilical cord from which blood vessels are removed; b) subculturing the isolated mesenchymal stem cells 1 to 10 times in serum-free cell culture medium; and c) filtering after culture medium is obtained in the subculturing step, as stated supra, the specification describes only subculturing three times or four times, and then, when the confluency of the cells reached 70% to 80%, the culture medium was replaced with phenol-red free MEM-alpha containing 5% human platelet lysate (HPL) and 1 % P/S, followed by culturing for 48 hours, to separate a culture medium. Which was filtered with a 0.22 μm filter.
Accordingly, Applicant did not demonstrate a reduction to practice of a method of improving a skin condition in a subject, with any type of umbilical cord-derived stem cell, using a culture media made and characterized by any means.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of practicing the claimed invention is not well established. Although methods for improving skin conditions comprising the administration of UC-MSC conditioned culture media were known, and the proteins claimed to be in conditioned culture media were known in the prior art, one of skill in the art would neither expect nor predict a successful outcome for a method of improving a skin condition in a subject comprising a strengthened skin barrier with increased expression of AQP3, HAS-2 and/or HAS-3, comprising administering an umbilical cord-derived mesenchymal stem cell culture media as the active ingredient as claimed.
The following describes the state of the art with respect to methods for making and using a UC-MSC conditioned culture media to improve skin conditions.
Firstly, Kim et al. (Biochem Biophys Rep, 2018, 96-102, see IDS filed 4/14/2026) teach a method of improving skin condition comprising applying an umbilical cord-derived mesenchymal stem cell culture media in vitro to dermal fibroblasts to stimulate growth and extracellular matrix production, and in vivo to reduce wrinkles and increase dermal density (Abstract). Importantly, using the RayBiotech array similar or identical to Applicant’s, Kim (2018) analyzed the presence of an array of proteins secreted in umbilical cord-derived mesenchymal stem cell culture media and did not find the 71 protein as claimed (see Fig. 1A). Thus, Kim (2018) established that despite making a UC-MSC conditioned culture media and using the same or similar techniques described in Applicant’s specification to characterize said media, the ordinary artisan could not predictably arrive at the claimed cell culture media product arising from the disclosed process.
Furthermore, Kim (2018) teaches that the expression level of the proteins detected by said array are significantly affected by the media used and the time the UC-MSCs are in culture. Specifically, Kim (2018) demonstrates that a culture media supplemented with as little as 10ng/ml EGF shows up on the array at time 0 hr (see Fig. 1B). Thus, Kim (2018) established that the starting materials used for making UC-MSC conditioned media are critical for establishing the final presence and composition ratios of the proteins in the conditioned media. Note that as stated supra, Applicant’s uses a distinct primary UC-MSC cell type isolated and subcultured by a specific method at a specific range of confluence (70-80%) with a specific starting media of MEM-alpha and 5% human platelet lysate.
Moreover, in regard to the effects of 5% human platelet lysate (HPL) on the composition ratio of a UC-MSC conditioned culture media, as a first matter, it well known HPL is a complex mixture of numerous cytokines and growth factors that would contribute to the composition ratio of the final conditioned culture media. Furthermore, Weiss et al. (WO2017/132358) teaches and claims methods of producing UC-MSCs and has demonstrated 5% HPL significantly effects UC-MSC cell proliferation by orders of magnitude as well as cell viability (pgs. 16-17, MSC Expansion Comparison, see Fig. 3), which would also be expected to effect the final conditioned culture media.
Second, Kim (2018) demonstrates that the measured composition ratios of the proteins in the UC-MSC conditions media change over time in culture. Specifically, Kim shows that as little as a 12 hour difference in culture time can have a significant impact on the composition ratio of a protein in the conditioned media (see Fig. 1B). Thus, Kim (2018) established that that the composition ratios of the proteins in the UC-MSC conditions media are highly dependent on the time in culture. Note that as stated supra, Applicant’s uses a distinct UC-MSC with a specific starting media for 48 hours.
Third, as far as culture conditions influencing the making and using UC-MSC conditioned culture media, Miranda et al. (Frontiers Immuno, 2019 10:1-14) teaches that secretome profile and therapeutic potential of the condition media changed depending on the culture conditions. Similar to Kim, Miranda makes a conditioned media from UC-MSCs, but Miranda teach the resulting media only comprises one (FGF-2) of the 71 proteins as claimed. Specifically, Miranda cultured UC-MSC on a 2D monolayer versus a 3D spinner-flask after 48 hours of conditioning, wherein the spinner-flask conditioned media was characterized by a prevailing expression of anti-inflammatory cytokines such as IL-10 and LIF, along with trophic factors involved in different mechanisms leading to tissue regeneration, such as PDGF-BB, FGF-2, I-309, SCF, and GM-CSF, while the static 2D monolayer derived conditioned media contained relatively higher levels of pro-inflammatory cytokines IL-6, MCP-1, and IL-21 (Abstract, p. 6. Fig. 2). Thus, Miranda established that that the composition ratios of the proteins in the UC-MSC conditions media are highly dependent on the static or dynamic culture conditions. Note that as stated supra, Applicant’s uses a distinct UC-MSC with a specific starting media for specific time, but does not describe the culture conditions with sufficient detail to permit the ordinary artisan to immediately envisage the claimed culture media product arising from the disclosed process.
Fourth, the prior art of Shen et al (Mol Med Rep, 2015, 12:20-30) teaches a method of treating a skin condition comprising administering a composition comprising human umbilical cord-derived mesenchymal stem cell (UC-MSC) culture medium to a subject’s skin (Abstract). Furthermore, Shen teaches the active steps for preparing the UC-MSC-CM comprising: a) isolating MSCs from human umbilical cord from Wharton’s jelly (which does not include the arteries and veins), b) culturing the UC-MSCs in serum-free DMEM for 72 hours, c) ultrafiltration of the condition media through a 0.22 micron filter (p. 21, Materials and Methods). However, when Shen examines presence of cytokines and growth factors present in the conditioned media, only one protein (FGF-2) is shared with the 71 proteins claimed (Table 1). Thus, Shen establishes that that the composition ratios of the proteins in the UC-MSC conditions media are highly variable and depend on the UC-MSC isolation conditions and the methods of detection. Note that as stated supra, Applicant’s uses a distinct UC-MSC with a specific starting media for specific time, with specific procedures for isolating and subculturing the UC-MSC, but relies on a single proprietary commercial kit from RayBio for detecting the 71 cytokines and their composition ratios from a single conditioned culture media sample with no accounting for batch to batch variations, nor control media that had not been exposed to cells. Again, instant specification does not describe the detection methods with sufficient detail to permit the ordinary artisan to immediately envisage the claimed culture media product arising from the disclosed process.
Fifth, the post filing review of Li et al. (Cell Proliferation, 2024;57:1-16) evidences that the UC-MSC secretome found in conditioned media is a complex mixture of proteins released by a variety of ways including exosomes, microvesicles, and apoptotic bodies (see Fig. 1), and the nature of the secretome is influenced by the UC-MSC source, culture conditions, separation method, identification technique, storage, and pretreatment of cells (Abstract, pgs. 9-11, Section 4, see Table 1). This post filing evidence, coupled with Applicant’s admission that “the composition ratio of proteins, rather than the mere presence or absence of individual proteins, that determines the biological activity of a culture media, and … a completely different cellular response may be induced when the expression levels and composition ratios of the key factor differ, which means that the efficacy of a culture medium is determined not merely by a list of its constituents components but by their quantitative balance” evidence that the instant specification has not sufficiently described how to make the active ingredient of the claimed invention.
Applicant has claimed a genus of methods to improve skin conditions in a subject that strengthen barrier function by increasing expression of AQP3, HAS-2, and/or HAS-3 comprising administering a UC-MSC conditioned culture comprising a distinct combination of 71 different cytokines and growth factors at a distinct composition ratio, yet the specification has not disclosed such methods in a subject, has not set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of methods, and has not provided sufficient detail to permit the ordinary artisan to immediately envisage the claimed culture media product arising from the disclosed process. Furthermore, the state of the art indicated that practicing the claimed method is not well established with the claimed function in successfully improving skin conditions in a subject with the claimed UC-MSC conditioned culture media would require undue experimentation.
Since the prior art at the effective filing date of the present application did not provide guidance to improve skin conditions in a subject that strengthen barrier function by increasing expression of AQP3, HAS-2, and/or HAS-3 comprising administering a UC-MSC conditioned culture comprising a distinct combination of 71 different cytokines and growth factors at a distinct composition ratio, it is incumbent upon the instant specification to do so. The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention.
CONCLUSION
In conclusion, since the art teaches that success of said method is prone to influence by multiple factors, and is highly unpredictable with respect to making and using the UC-MSC conditioned culture media as claimed with the essential composition ratio, and the specification does not provide ample guidance with respect to achieving the unexpected results, one would be burdened with undue experimentation to make and use the claimed invention for improving a skin condition in a subject comprising administering the UC-MSC culture media as the active ingredient. Given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is require to make and use the invention beyond the scope of administering a particular UC-MSC conditioned culture media comprising a specific composition ratio of the 71 proteins that are derived from a specific type of UC-MSC that is processed and detected by a particular means.
Conclusion
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 extension fee 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 date of this final action.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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