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 .
Response to Amendment
Applicant's amendment and argument filed 12/19/2025, in response to the non-final rejection, are acknowledged and have been fully considered. Any previous rejection or objection not mentioned herein is withdrawn.
Claims 5, 7-8, 11, 14-19 are pending of which claims 7-8 and 11 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/12/2024.
Claims 5 and 14-19 are being examined on the merits.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 5, 14, 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kim Su et. al. (KR20170044999A), hereinafter Su, Naughton (US8530415B2) and European Medicines Agency, (Committee for Human Medicinal Products, 09 October 2017, pages 1-8). This rejection is maintained due to the arguments and amendments filed on 12/19/2025.
Su’s general disclosure is to compositions for improving skin and preventing hair loss (see abstract).
Su teaches “A pharmaceutical composition for treating a wound comprising an adult stem cell or an exosome derived from the culture as an active ingredient” (see claim 1).
Su teaches “In the present invention, an exosome refers to a small follicle having a membrane structure that is secreted from various cells. The diameter of the exosome is approximately 30 to 1,000 nm, which means the follicle that is fused to the plasma membrane and released to the extracellular environment. Representative expression markers of exosomes correspond to HSP70, CD63 and CD9” (see page 8, last para.). Su teaches the composition to be used in cosmetics and to have buffers (see last para. page 9 and 2nd para. page 10) and preservatives (see 2nd para. page 9). Su also teaches wherein the exosomes are contained in an amount of 1 x 107 to 1 x 1012/ml (see claim 4).
Regarding claim 14, Su teaches the composition to further comprise a chelating agent (see 2nd para. page 10).
Su does not specifically teach that the cell is from a human dermal fibroblast.
Naughton’s general disclosure is to a method of producing embryonic proteins (see abstract).
Regarding claim 5, Naughton teaches “A tissue regeneration patch comprising a composition made by culturing fibroblast cells under hypoxic conditions for at least 2 weeks on a microcarrier bead or three-dimensional surface in a suitable growth medium containing basic FGF (bFGF), under 1-5% oxygen thereby producing multipotent stem cells, wherein the multipotent stem cells produce and secrete a soluble composition, collecting the composition after said 2 weeks and preparing a tissue regeneration patch comprising the soluble composition” (see claim 1).
Naughton also teaches after inoculation of the three-dimensional scaffolds, the cell culture is incubated in an appropriate nutrient medium and incubation conditions that supports growth of cells into the three-dimensional tissues. Additionally, the same media can be used for both hypoxic and aerobic cultivation. In one aspect, the growth media is changed from serum-based media to serum free media after seeding and the first week of growth (see column 17, lines 1-4 and 33-36).
Naughton discusses wherein other materials have also been used for soft tissue repair or augmentation, such as lactic acid-based polymer blends (see column 2, lines 4-10 and column 9, lines 19 and 32-38) and wherein some aspects the microcarriers comprise hydrogels which are typically hydrophilic polymer networks filled with water (see column 12, lines 6-9).
Naughton “In another embodiment, the present invention provides a method of producing a Wnt protein and a vascular endothelial growth factor (VEGF). The method includes culturing cells under hypoxic conditions on a surface (e.g., two-dimensional or three-dimensional) in a suitable growth medium, thereby producing the Wnt protein” and wherein the Wnt protein is Wnt3a (see summary of the invention, 3rd para. and Table 4, column 29). Naughton teaches the cells to be fibroblasts grown in these conditions (see Table 3, Table 4, Table 5, page columns 29-30).
Regarding to claims 5 and 16-18, pertaining to wherein the ECVs when tested using a western blot analysis demonstrates an absence of a Wnt7a or a Wnt7b protein and further comprises exosomes with a Wnt3a protein within the exosome, these limitations appear to be inherent to the culturing conditions as described and recognized by the applicant. The applicant recites “the specific protein composition of human ECV composition derived from a soluble CCM produced by HDFs cultured under hypoxic conditions of about 1-5% was examined by western blot analysis. Western blot analysis using an anti-Wnt3a antibody (Santa Cruz #26358), an anti-Wnt7a antibody (Santa Cruz #26361-P) and an anti-Wnt7b antibody (Santa Cruz #sc-26363) demonstrated the presence of Wnt-3a in the ECVs and the absence of Wnt7a and Wnt7b (Figures 5A-C). This data suggests that Wnt 3a is secreted into the CCM and that Wnt-3a is also stored or encompassed and released into ECVs” (see 0232).
Regarding claim 15, Naughton teaches wherein the cells to be human neonatal foreskin fibroblasts (see example 1, column 28, example 2, column 31 and column 12 lines 27-30).
Regarding the limitation wherein the exosome composition when tested using western blot analysis demonstrates an absence of a Wnt7a and Wnt7b protein, this appears to be a matter of judicious selection. Naughton teaches “In still other aspects, the soluble fraction is subject to chromatography to remove salts, impurities, or fractionate various components of the medium. Various chromatographic techniques may be employed, such as molecular sieving, ion exchange, reverse phase, and affinity chromatographic techniques. For processing conditioned medium without significant loss of bioactivity, mild chromatographic media may be used. Non-limiting examples include, among others, dextran, agarose, polyacrylamide based separation media (e.g., available under various tradenames, such as Sephadex, Sepharose, and Sephacryl)” (see column 22, lines 1-11). Furthermore, Naughton’s disclosure in the abstract states “the present invention is directed to a method of producing compositions including embryonic proteins. The method includes culturing cells under hypoxic conditions on a biocompatible three-dimensional surface in vitro. The culturing method produces both soluble and non-soluble fractions, which may be used separately or in combination to obtain physiologically acceptable compositions useful in a variety of medical and therapeutic applications”. Thus creating the same composition and removing certain soluble proteins is a matter of judicious selection and would have been prima facie obvious given the relied upon art.
European Medicines Agency teaches that benzyl alcohol is used as an excipient for its preservative properties for cutaneous use (see page 3, 1. 2nd para.) and is mainly used in medicinal products that intramuscularly, such as antibiotics, anti-inflammatory or antipsychotic medicines where its anaesthetic properties reduce pain at the injection site. Benzyl alcohol is also present in medicinal products administered intravenously (anti-cancer drugs, heparins, cardiovascular drugs). Finally, benzyl alcohol is used as a preservative in many topical preparations, such as antifungal and anti-inflammatory products” (see page 3, 2.)
Therefore it would have been obvious to persons having skill in the art and before the effective filing date to use human dermal fibroblasts as taught by Naughton in the invention disclosed by Su because as Naughton teaches these growing conditions produce multipotent stem cells and Su teaches that the exosomes from those stem cells would have the same markers as described for the same effects. Additionally, the same culturing conditions as recognized by the applicant should create exosomes which would lack Wnt7a and Wnt7b.
It would have also been obvious to select benzyl alcohol as the preservative because as the European Medicines Agency teaches it is widely used as an excipient which also acts as a preservative in medicinal products and as topical preparations.
It would have additionally been obvious to optimize the exosome amount to be within the amount being claimed because Su teaches overlapping effective ranges and this amount is an optimization well within the purview of any skilled artisan, given the information taught in the prior art.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ composition with the composition of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed product and the product of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Furthermore, regarding the exosome composition demonstrating a lack of Wnt7a and Wnt7b proteins, this appears to be a matter of mere judicious selection as can be appreciated by Naughton’s on teaching. Naughton teaches of known methods for removing various fractions and impurities through the use of chromatography etc. and so removing Wnt7a and Wnt7b from the exosome composition is well within the purview of any skilled artisan. For example one would want to remove Wnt7a and Wnt7b as these proteins are known in the art to be associated with certain cancers (such as breast, pancreatic and head/neck). This is also made apparent in the prior art as Naughton teaches “The ECM compositions described herein can include various Wnt factors. Wnt family factors are signaling molecules having roles in a myriad of cellular pathways and cell-cell interaction processes. Wnt signaling has been implicated in tumorigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation, and Alzheimer’s disease” (see column 20, lines 38-45).
There would have been a reasonable expectation of success in arriving at the instant invention given the prior art because the art recognizes the culturing conditions needed to induce excretion of exosomes having CD63, CD9 and Wnt3a expression.
Response to Arguments
Applicant's arguments filed 12/19/2025 have been fully considered but they are not persuasive. The applicant argues that Su does not teach that the exosomes are from human dermal fibroblasts cells or human neonatal foreskin fibroblasts cells or that the composition when tested with western blot analysis show an absence of Wnt7a/7b proteins. Please note, since the Office does not have the facilities for examining and comparing applicants’ composition with the composition of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed product and the product of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972). Also the Office relies on Naughton to show wherein the cells can be human neonatal foreskin fibroblasts (see example 1, column 28, example 2, column 31 and column 12 lines 27-30).
Naughton teaches methods for obtaining an exosome composition comprising of the same components as being taught of the instant invention. Naughton is inventors of both the prior art and the instant invention. Naughton of the prior art explains how to obtain the topical exosome composition by the same methods and describes methods for removing various elements through chromatography. Thus it appears to be a matter of judicious selection when removing Wnt7a and Wnt7b or as pointed out in the above rejection can be for reasons that these proteins are known in the art to be associated with certain cancers and removal of these proteins are for safety concerns.
The applicant argues that they recognize that Naughton of the prior art teaches how to create the exosome composition by culturing human fibroblasts under hypoxic conditions to produce an ECM and the ECM comprises soluble and insoluble fractions which contain a wide variety of materials such as Wnt factors etc., but there is no teaching of a composition which does not include the Wnt7a and Wnt7b proteins. As discussed in the above rejection the decision to exclude the Wnt7a and Wnt7b proteins can be due to cancer safety concerns and/or a matter of judicious selection as the inventions appear to be effective for the same purpose. The instantly claimed composition which is obtained through growth media would include the exact same components as can be appreciated by the applicant’s own work (see table 4 of instant specifications and table 4 of the prior art). Both tables describe the differential Wnt expression in hypoxic three-dimensional fibroblasts cultures and both tables are the exact same. Naughton teaches of ways to remove unwanted components using chromatography and it would have been obvious to remove the Wnt7a and Wnt7b for reasons just explained. The instant composition would appear to be directed to stimulating hair growth and that is what the prior art teaches the compositions to be useful for. Unless shown some improvement over the prior art through removing the Wnt7a and Wnt7b proteins or some showing of criticality this would only appear to be a matter of judicious selection.
Conclusion
Currently no claims are allowed.
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.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655