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
Acknowledgement is made of Applicants’ claim for benefit to US Provisional application 63/738005 (filed 12/23/2024).
Election/Restrictions
Applicant’s election of Group I, drawn to a composition comprising human mesenchymal conditioned media from BM-MSCs, UC-MSCs and fibroblasts, in the reply filed on 7/2/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 1-21 read on the elected invention and have been considered on the merits. Claims 22-23 are withdrawn from consideration.
Claim Interpretation
Claim 1 is directed to a composition comprising human mesenchymal conditioned media from human-derived cell sources. The human derived-cell sources are: BM-MSCs, UC-MSCs and fibroblasts. The claim is interpreted as a composition comprising a combination of conditioned media from all three of human BM-MSCs, human UC-MSCs, and human fibroblasts.
Conditioned medium is produced by culturing cells in a cell culture media for a period of time, such that the cells release various proteins, cytokines, etc, into the culture media. The conditioned media will include the culture media in which the cells are cultured, as well as the cellular products secreted by the cells during culture.
Claim 1 defines the medium in which each of the BM-MSCs, UC-MSCs and human fibroblasts are grown. While these are product-by-process limitations (directed to how the cells are cultured), they are limiting to the final conditioned media, as the final conditioned media will contain the culture media in which the cells are cultured (as above).
The recitation at lines 4-6, “wherein the BM-MSCs, UC-MSCs, and fibroblast cells are cultured in growth media specifically formulated for optimal cell proliferation and optimized for the secretion of regenerative molecules” does not provide any meaningful limitation, as it provides no details on the actual growth medias.
Lines 7-9 of the claim are understood to require the BM-MSCs to have been cultured in DMEM-F12, supplemented with FBS and growth factors. Thus the BM-MSC conditioned media-portion of the claimed composition will comprise DMEM-F12, FBS, growth factors and at least some cellular products secreted by the hBM-MSCs.
Lines 10-12 of the claim are understood to require the UC-MSCs to have been cultured in DMEM-F12, supplemented with FBS and growth factors. Thus the UC-MSC conditioned media-portion of the claimed composition will comprise DMEM-F12, FBS, growth factors, and at least some cellular products secreted by the hUC-MSCs.
Lines 13-14 of the claim are understood to require the fibroblasts to have been cultured in DMEM + 8% FBS. Thus the human fibroblast-conditioned media-portion of the claimed composition will comprise DMEM, FBS and at least some cellular products secreted by the human fibroblasts.
The claim does not limit the ratio of BM-MSC-conditioned media : UC-MSC-conditioned media : fibroblast-conditioned media.
The broadest reasonable interpretation of the claims treats the growth factors listed in parentheses as non-limiting examples.
In claim 4, the broadest reasonable interpretation of the claim treats the limitations listed as “in certain embodiments” (i.e. lines 4-11) as exemplary and thus non-limiting.
Claim 5 is being interpreted as further requiring the composition to contain 1% preservative comprising 1% EUXYL at room temperature.
Claim 6 is being interpreted as further requiring the composition to contain 3% sterile glycerol and freezing at -80oC in low-temperature-resistant containers.
Claim 7 states the composition is used to create formulations consisting of Compositions A, B, C and D. This claim is interpreted as reciting intended uses of the claimed composition. In this case the recited intended use does not further limit the composition of claim 1.
Claims 8-21 further define the formulation(s) that can be created using the composition of claim 1. Claims 8-21 do not further limit the composition of claim 1.
Claim Objections
Claims 1, 10, 11, 13, 14, 16, 17, 19 and 20 are objected to for minor informalities: In claim 1, at line 10, there appears to be a typographical error: the phrase “growth factors for UC-MSC…” should be amended as “growth media for UC-MSC…”
Each of claims 10, 11, 13, 14, 16, 17, 19 and 20 recite the phrase “Human Mesenchymal Human Mesenchymal Conditioned Media”. This appears to be typographical error and should be amended to “Human Mesenchymal
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 1 and 4-21 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.
Regarding claim 1: At lines 8-9 and 11-12, the claim recites “growth factors (rhFGF basic, IGF-1)” and “growth factor (rhEGF, rhFGF basic, rhFGF acidic)”, respectively. In each instance “growth factors” covers a genus, and then the specific growth factors provided in parenthesis are species within that genus. It is unclear if the claim whether the species in the parentheses are part of the claimed invention, or merely exemplary. See MPEP § 2173.05(d). Overall, the metes and bounds of the claim are unclear because it is unknown if the claim requires inclusion of generic growth factors, or if the claim requires the inclusion of the specific growth factors. The broadest reasonable interpretation only requires the presence of generic growth factors.
Claims 2 and 3 further specify the growth factor content of the BM-MSC and UC-MSC media, respectively, and thus clarify the scope and are not included in the rejection. However, claims 4-21 depend from claim 1, do not otherwise clarify the issue, and thus are rejected on the same basis.
Regarding claim 4: Claim 4 is held to be indefinite because it is not clear if the requirements at lines 4-11 are limitations to the composition, or merely exemplary. Specifically, the language “wherein certain embodiments…specifically comprise….” is problematic because it is unclear if this is a firm limitation, or an example. The broadest reasonable interpretation will only require the BM-MSCs, UC-MSCs and fibroblasts to be cultured in the presence of an antibiotic/antimycotic solution comprising penicillin, streptomycin, amphotericin or hygromycin.
Regarding claim 5: Claim 5 contains the trademark/trade name EUXYL. 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, it appears the trademark/trade name is used to identify/describe a preservative composition and, accordingly, the identification/description is indefinite.
Regarding claims 7-21: Claims 7-21 recite intended use of the claimed composition. As such, claims 7-21 does not further limit the composition of claim 1 (See rejection under 35 USC 112(d) below). However, for purposes of compact prosecution, the following comments are made regarding claims 7-21:
In claim 7 “Compositions A, B, C and D” are undefined. The specification does not provide for explicit definitions of these compositions. It is also unclear if the composition [of claim 1] is to be used to create a formulation consisting of the combination of Compositions A, B, C and D, or if the composition [of claim 1] is to be used to create a formulation consisting of any one of Compositions A, B, C and D.
In claim 8, it is unclear the additional recited components are part of Compositions A, B, C or D, or if they are in addition thereto. If in addition thereto, it is problematic, as the language in parent claim 7 refers to compositions consisting of Compositions A, B, C and D. The use of the closed transitional phrase “consisting of” excludes the presence of any additional component.
Likewise, claims 9-21 each further define the Compositions A, B, C or D as comprising the recited ingredients. This does not properly correlate with the parent claim 7 language that states the formulations consist of Compositions A, B, C and D.
In claims 12, 15, 18 and 20 the content of the tables is unclear. The left hand column recites various ingredients, some of which are provided with a percentage. However, the right hand column recites different percentages. It is thus unclear what the percentages in the left hand column relate to. It is also noted that several ingredients are listed multiple times in the left hand column (e.g. water).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7-21 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 states the composition is used to create formulations consisting of Compositions A, B, C and D. This claim is interpreted as reciting intended uses of the claimed composition. In this case the recited intended use does not further limit the composition of claim 1.
Claims 8-21 further define the formulation(s) that can be created using the composition of claim 1. Claims 8-21 do not further limit the composition of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Wijenthiran et al (WO 20/130800), in view of Carava et al (EP 4461292), Amirthalingam et al (J Stem Cell Res Dev, 2019), and further in view of Freshney (Culture of Animal cells: A Manual of Basic Technique, 2000).
Wijenthiran et al disclose stem cell conditioned media for clinical and cosmetic applications (See Pg. 1, ln 5-6). The stem cell-conditioned medium can comprise (a) a stem cell conditioned medium containing extracellular factors, and (b) a carrier oil, wherein the extracellular factors are encapsulated by the carrier oil (See Pg 1, ln 29-32, and claim 1). The stem cell-conditioned media can further comprise (c) extracellular factors from mature fibroblasts (See Pg 3, ln 10-20 and claims 6-9). The extracellular factors from fibroblasts are derived from conditioned culture media from the fibroblasts (See Pg 4, ln 4-13). The stem cells used to condition the media are mesenchymal stem cells (MSCs). The MSCs may be human, from, inter alia, bone marrow, umbilical cord, and combinations thereof (See Pg 2, ln 31-Pg 3, ln 3 and claims 2-3).
Regarding claim 1: Wijenthiran et al thus discloses a composition for cosmetic application that comprises conditioned medium from a combination of human bone marrow-MSCs, human umbilical cord MSCs and human fibroblasts.
The content (defined by the growth medium) of each individual component will be addressed:
Regarding the conditioned medium from human umbilical cord MSCs: At the detailed protocol at Pg 7-8, Wijenthiran et al exemplifies production and collection of conditioned medium from Whartons Jelly stem cells (which read on human UC-MSCs). Notably, the Wharton’s jelly stem cells are cultured in cell culture medium (CCM) comprising DMEM-KO supplemented with 10% FBS, gentamicin and 100X glutamax (See Pg 8, ln 20-28). Thus the conditioned media from human Wharton’s jelly stem cell (human UC-MSCs) contained DMEM and FBS. Official notice is taken that FBS contains growth factors.
Wijenthiran et al differ from the claim in that they use DMEM-KO, not DMEM-F12. However, at the time the application was both DMEM and DMEM-F12 were recognized as suitable basal culture media. See Freshney at Pg. 94 “Complete Media”. Freshney teach that a 1:1 ratio of DMEM-F12 optimizes the richness of F12 and the higher nutrient content of DMEM and is suitable for many different cell types. Therefore, given that both DMEM and DMEM-F12 were recognized as suitable basal media for many cell types, it would have been prima facie obvious to have substituted DMEM-F12 for the DMEM component used in Wijenthiran et al. Substitution of one known element for another known element, the elements having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See MPEP 2143(I)(B).
As such, Wijenthiran et al render obvious a conditioned media from human umbilical cord MSCs comprises DMEM-F12, and FBS, wherein the FBS contains growth factors.
Regarding the conditioned medium from human fibroblasts: At the detailed protocol at Pg 10-12, Wijenthiran et al exemplifies production and collection of conditioned medium from human foreskin fibroblasts. Notably, the foreskin fibroblasts are cultured in “FSF culture media” (See Pg 11, ln 28-Pg 12, ln 8). Wijenthiran et al does not provide the recipe for “FSF culture media”.
Because Wijenthiran et al does not provide details of the “FSF culture media”, it would have been prima facie obvious for one to look to the prior art to determine an appropriate culture media for producing a fibroblast-conditioned culture media. Carava et al is referenced to provide details regarding suitable growth media for human fibroblasts when the goal is to provide conditioned media for cosmetic applications (See ¶0012). Carava et al disclose culturing human fibroblasts in medium comprising DMEM, FBS, glutamine, and sodium pyruvate (See Example 1, ¶0073-0082). The FBS is present at 8.8% (v/v). As such, it would have been prima facie obvious to have used the medium comprising DMEM, FBS, glutamine and sodium pyruvate of Carava et al for the “FSF culture media” in the method of Wijenthiran et al. This conclusion of obviousness is based off a teaching in the art.
As such, Wijenthiran et al render obvious a conditioned media from human fibroblasts comprising DMEM and approximately 8% FBS.
Regarding the conditioned medium from human BM-MSCs: despite disclosing its suitability for inclusion, Wijenthiran et al does not exemplify production of conditioned media from human BM-MSCs.
Because Wijenthiran et al does not provide details producing conditioned media from human BM-MSCs it would have been prima facie obvious for one to look to the prior art to determine an appropriate culture media for producing a BM-MSC-conditioned culture media suitable for cosmetic purposes. Amirthalingam et al discloses culturing human BM-MSCs to produce conditioned culture media suitable for cosmetic skin care use (See title). Specifically, Amirthalingam et al culture hBM-MSCs in DMEM-KO, FBS, bFGF and glutamax (See Pg 2 “Mesenchymal stem cell culture and conditioned media preparation”).
It is noted Amirthalingam et al DMEM-KO instead of DMEM-F12. However, for the reasons set forth above, substitution of DMEM-F12 for DMEM-KO would have been prima facie obvious in view of Freshney et al.
As such, it would have been prima facie obvious to have used the protocol of Amirthalingam et al, but including DMEM-F12 in place of DMEM-KO, to produce hBM-MSC-conditioned media for inclusion in the composition of Wijenthiran et al. This conclusion of obviousness is based off a teaching in the art.
As such, Wijenthiran et al and Amirthalingam et al render obvious a conditioned media from human BM-MSCs comprising DMEM-F12, FBS and bFGF (growth factors).
Regarding claim 4: Following the discussion of claim 1 above, Wijenthiran et al teach inclusion of gentamicin with at least the WJ stem cells (See Pg 8, ln 21), and ‘antibiotic-antimycotic’ was included with the fibroblast (See Pg 10, ln 31). Thus at least gentamicin will be present in the combined conditioned media.
Wijenthiran et al differs from the instant claim in that they do no teach one of the four antibiotics/antimycotics claimed. However, official notice is taken that each of penicillin, streptomycin, amphotericin and hygromycin were well known antibiotics suitable for use in cell-cultures and were each recognized as functional equivalents (as far as providing antibiotic protection to ac ell culture) as gentamicin. As such, substitution of any one or more of the antibiotics claimed for gentamicin would have bene prima facie obvious. One would have had a reasonable expectation that substitution of any one of the claimed antibiotics would serve equivalently to gentamicin to protect against bacterial growth in the composition.
Regarding claim 5: Following the discussion of claim 1 above, Wijenthiran et al teach that the stem cell conditioned media composition can be formulated into a facial treatment serum. The formulation is shown in Table 13 (See Pg. 30-34). The serum formulation contains, inter alia, phenoxyethanol, ethylhexylglycerine (EUXYL) at 1%.
Regarding claim 6: Following the discussion of claim 1 above, Wijenthiran et al teach the stem cell conditioned media composition can be cryopreserved (See Pg 14, ln 20-32). To cryopreserve, the composition is mixed with cryopreservative, then deep frozen at -85oC. Wijenthiran et al use FBS and DMSO as the cryopreservative agent. Official notice is taken that glycerol is an alternative cryopreservative agent that has equivalent function to DMSO. It therefore would have bene prima facie obvious to have substituted 3% glycerol for the DMSO in the method of Wijenthiran eta l. One would have had a reasonable expectation that inclusion of an appropriate amount of glycerol would successfully permitted cryopreservation of the stem cell conditioned medium in a manner equivalent to DMSO.
Allowable Subject Matter
Claims 2 and 3 are 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.
Claim 2, in so far as it is interpreted as being directed to a composition comprising human mesenchymal conditioned media from human-derived cell sources, wherein the human-derived cell sources comprise BM-MSCs, UC-MSCs and fibroblasts,
wherein the conditioned media from BM-MSCs is produced by culturing BM-MSCs in growth media containing DMEM-F12 supplemented with 10% FBS, 15 ng/mL IGF-1, 125 pg/mL rhFGF basic, and 2.4 mM L-alanyl-L-glutamine,
wherein the conditioned media from UC-MSCs is produced by culturing UC-MSCs in growth media containing DMEM-F12 supplemented with FBS and growth factors, and
wherein the conditioned media from fibroblasts is produced by culturing fibroblasts in growth media containing DMEM with 8% FBS, is free of the art.
Claim 3, in so far as it is interpreted as being directed to a composition comprising human mesenchymal conditioned media from human-derived cell sources, wherein the human-derived cell sources comprise BM-MSCs, UC-MSCs and fibroblasts,
wherein the conditioned media from BM-MSCs is produced by culturing BM-MSCs in growth media containing DMEM-F12 supplemented with FBS and growth factors,
wherein the conditioned media from UC-MSCs is produced by culturing UC-MSCs in growth media containing 4% FBS, 5 ng/mL rhFGF basic, 5 ng/mL rhFGF acidic, 5 ng/mL rhEGF and 2.4 mM L-alanyl-L-glutamine, and
wherein the conditioned media from fibroblasts is produced by culturing fibroblasts in growth media containing DMEM with 8% FBS, is free of the art.
The prior art does not teach or suggest these details.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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