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 .
Applicant's arguments filed 12/23/2025, in response to the final rejection, are acknowledged and have been fully considered. Any previous rejection or objection not mentioned herein is withdrawn.
Claims 1-5, 7-10, 16-19 and 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 1-5, 7-10 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et. al. (From IDS, Protective effects of adipose-derived stem cells secretome on human dermal fibroblasts from ageing damages, Int J Clin Exp Pathol 2015; 8(12): 15739-15748), Patrick Tonnard et. al. (Nanofat Grafting: Basic Research and Clinical Applications, Plastic and Reconstructive Surgery, Vol 132, No. 4, 1017-1026, October 2013), Nie Yunfei and Zhang Linghua (CN109876189A) hereinafter Yunfei with support from Yu et. al. (Fat extract promotes angiogenesis in a murine model of limb ischemia: a novel cell-free therapeutic strategy, Stem Cell Research and Therapy, 9, 294, 08-Nov-2018). This rejection is maintained with slight modifications due to the arguments filed on 12/23/2025.
Regarding claims 1-4, Wang teaches adipose-derived stem cells (ADSCs) have gained popularity in anti-ageing field, which may provide promising methods to fight against skin ageing.
We irradiated human dermal fibroblasts (HDFs) with UVB at different senescent levels, and then treated them with ADSC-CM. After 48 h, we detected cellular proliferative activity, morphology, SA-β-Gal expression, apoptosis, mRNA expression of collagen I, collagen III and elastin (see abstract).
Recent studies have reported ADSCs may act as an effective therapy ADSCs fight against ageing damages for cutaneous photoageing both in vivo and in vitro (see page 15739 last para to 15740 first para.).
In our group, human dermal fibroblasts (HDFs) at different senescent levels were exposed to UVB then cultured in conditioned medium of ADSCs (ADSC-CM) that contains the whole raw secretome of and takes advantages of easier storage and safer application over ADSCs. Afterwards we detected related biochemical indexes, aiming at more comprehensively observing the ageing characteristics of HDFs as well as evaluating the antiageing effects of ADSCs secretome (see page 15740 second para.).
Wang teaches obtaining fat tissue (human lipoaspirate), washing in phosphate buffered saline and mincing finely, discarding supernatant and collecting the pellet (see 15740 materials and methods, first para.).
Regarding claim 6, Wang does not require there to be any cells or lipid droplets, only the components within the ADSCs which is the raw secretome.
Regarding claim 7, Wang teaches that the active components is the secretome of the ADSCs and thus it is obvious to use only those components without the use of any additionally added components.
Regarding claim 8, Wang teaches the secretome of the ADSCs to comprise of (TGFβ), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), pigment epithelium-derived factor (PEDF) (see page 15745, left column).
Wang does not specifically teach subjecting the intermediate layer to mechanical emulsification to obtain a mechanically emulsified fat mixture, centrifuging to obtain an intermediate layer which is primary fat extract and filtering and sterilizing to obtain the fat extract.
Tonnard and Yunfei are relied upon to show the newly amended methods of instant claim 1.
Tonnard’s general disclosure is to Nanofat grafting for clinical applications (see background, page 1017).
Tonnard teaches “the initial goal of fat grafting was to treat volume losses created by disease, trauma, or aging. Fat was injected with relatively large blunt cannulas (±2 mm diameter). For delicate areas such as eyelids and lips, smaller injection cannulas became popular. Lipofilling with cannulas as small as 0.7 mm in diameter, also called microfat grafting, has been described. For these indications, fat is harvested with small-hole cannulas to obtain a lipoaspirate with smaller fat particles. We previously described microfat grafting in the deep dermal layer of the skin with 23-gauge sharp needles for treatment of fine rhytides in the face. To work even more superficially with still finer sharp needles (27 gauge), the harvested fat was mechanically emulsified and filtered until a liquid suspension was obtained. We call this “nanofat.”” (see right column of 1017-1018 left column).
Yunfei also teaches the instantly claimed methods for obtaining a fat extract. Yunfei teaches providing a fat source adipose tissue and wherein the S1. adipose tissue is centrifuged to 1~8 min under the conditions of 1000~12000rpm, if being divided into three layers after centrifugation, is respectively pushed up Layer grease, middle layer mixture and bottom Tumescent fluid, then discard bottom Tumescent fluid, and filtering removal top layer grease simultaneously takes filtrate. S2. filtrate obtained by S1 non-contact ultrasonic is carried out to be crushed, the ultrasonication condition be 600~1190W, 5~ 55min, 20~38 DEG C. This process of ultrasonication would mechanically emulsify the fat mixture as claimed. S3. 3 will be centrifuged under the conditions of 1000~10000 rpm through the broken fat blend of S2 non-contact ultrasonic~ 10min, and centrifugation is discarded, collects the light-yellow floccule in upper layer to get the cell epimatrix material of cell factor is rich in (see claim 1).
Regarding claim 5, Yungfei teaches that the fat source components are useful for wound repair (see last para. of Background technique), which when considered in this context can be useful for a subject with a skin disease, when so broadly claimed because many subjects suffering from skin diseases would benefit from compositions that repair wounds of the skin.
Yu’s disclosure is relied upon to show that a fat tissue extract would contain the same components as claimed. Yu also shows the instant method steps for obtaining the fat extract and gives reasons to modify why one would optimize the extraction taught in Wang.
Yu teaches “In the current study, we aimed to produce a cell-free extract directly from human fat tissue and evaluate its potential therapeutic efficacy” (see abstract).
Yu teaches “the detailed procedures for isolating FE are shown in Fig. 1. The lipoaspirate was first rinsed with saline to remove red blood cells and then centrifuged at 1200 × for 3 min. After the first spin, the superior oily and inferior fluid layers were discarded, and the middle fat layer was g collected and mechanically emulsified. The emulsification was achieved via 30 passes of shifting the fat between two 10-cm syringes 3 connected by a female-to-female Luer-Lok connector (B. Braun Medical Inc., Melsungen, Germany). The emulsified fat was then frozen at − 80 °C and thawed at 37 °C for further disruption of the fat tissue. After one cycle of the freeze/thaw process, the fat was again centrifuged at 1200 × for 5 min. After a second spin, the fat was separated into four layers. The upper layer of oil was discarded; the second layer of g unbroken fat and the fourth layer of debris was discarded; and the third aqueous layer, namely the FE, was carefully aspirated without contamination of the bottom pellet. The final extract was produced by passing it through a 0.22-μm filter (Corning Glass Works, Corning, NY, USA) for sterilization and removal of cell debris” (see page 8 2nd para.). Here Yu teaches the same intermediate fat components as being claimed.
Yu also teaches “To verify the underlying mechanism of FE treatment, the angiogenic factors within FE were then measured in six samples using ELISA. High levels of growth factors, including BDNF, GDNF, TGF-β, HGF, bFGF, VEGF, PDGF, EGF, NT-3, and G-CSF, were detected in the FE (Fig. 4). The mean level and variation of each factor in the six samples are presented in Table 1” (see page 3).
Yu further teaches “ADSCs express a broad spectrum of paracrine factors that are known to be angiogenic, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin 6 (IL-6), and transforming growth factor alpha (TGF-α) [10]. Subsequent studies have confirmed that the administration of ADSC-conditioned medium (ADSC-CM) could also have efficient therapeutic effects on ischemic diseases [11, 12]. Thus, instead of cell transplantation, the delivery of ADSC-secreted factors has recently been considered an alternative strategy, as it can circumvent many safety concerns and limitations related to the use of cultured cells. However, the collection of ADSC-CM or its secretome for clinical application is still complicated and time consuming.
Adipose tissue has currently gained significant importance since it serves as an abundant source of ADSCs. As a result, adipose tissue and its derivatives, initially used for soft tissue augmentation, have now been used for regenerative purposes. For example, the autologous fat graft has been used to successfully treat irradiated tissue and chronic ischemia [13–17]. The stromal vascular fraction (SVF), a mixed cell population commonly isolated by the enzymatic digestion of fat, has been used in therapies for burn injury and diabetes [18, 19]. More recently, nanofat, a fat emulsion produced through mechanical forces, has been shown to improve fat graft survival and skin rejuvenation and has been used in the treatment of atrophic scars, among other conditions [20–25]. The regenerative effects of the aforementioned materials are considered mainly related to their cellular component via the secretion of growth factors. Interestingly, Sarkanen et al. [26] demonstrated that adipose tissue itself secretes large amounts of growth factors. After the incubation of adipose tissue for 24 h, the tissue culture medium contains numerous growth factors and cytokines that promote angiogenesis and adipogenesis in vitro and in vivo. Pallua et al. [27] found that fresh lipoaspirate contained a certain amount of proangiogenic factors, such as bFGF, VEGF, and platelet-derived growth factor (PDGF). These results indicate that adipose tissue is inherently enriched with a variety of bioactive factors that might be directly isolated for clinical application without the cell isolation or cultivation process.” (see background, para. 1-3).
“If the liquid portion contains a high level of growth factors, it might also possess therapeutic activity. More importantly, use of the cell-free liquid fraction could theoretically avoid the cell-related concerns in clinical applications; these concerns include the genetic stability of cells after processing, cell activity and survival after injection, and the storage of cells for multiple administration, as well as the immunogenicity of cells when using allogeneic fats. Based on these clues, we purified the liquid fraction, namely the “fat extract” (FE), from nanofat using a mechanical approach to remove the cellular components and the lipid remnants. We speculate that the cell-free aqueous component derived from fat may possess a similar proangiogenic function and exhibit therapeutic potential in reducing ischemic injury” (see background para. 3).
Therefore it is obvious that the same cell types would have the same markers as being claimed and it would be inherent to the extract itself especially if there was nothing done to optimize those said components. It would be expected that the same fat extract would have the same markers present and within similar amounts as this appears to be inherent to the fat extract itself.
It would have been obvious to persons skilled in the art before the effective filing date to adopt Yu and Yungfei’s methods in mechanically separating adipose tissue by first providing fat tissue and shredding the tissue as opposed to using blunt force as this is considered gentler to the cells. Centrifuging and rinsing the cut tissues would assist in eliminating any source in contamination. One can look to Yu or Yunfei to appreciate the order of operations and to see which layers need to be held and discarded (top and bottom layers). Yu and Yunfei also teach to emulsify after separation. Next since it is known that the adipocyte-derived stem cells are the components which are needed for the composition taught by Wang, as opposed to the stromal vascular fraction (SVF), one would want to centrifuge the emulsified layer to separate the adipocyte-derived stem cells from the SVF and follow it by filtering and sterilization to obtain an extract without any contaminants. It would have been obvious to substitute Wang’s method as just described because Yu and Yunfei teach a process which uses mechanical separation as opposed to enzymatic separation. Persons having skill would know that another centrifugation step would be needed during the method taught by Yu or Yunfei in order to separate out the adipocyte-derived stem cells from the SVF, which Yunfei is trying to maximize. It is further obvious to formulate the composition as a pharmaceutical composition as so broadly claimed because the composition is intended for pharmaceutical purposes.
Regarding claims 1 and 9-10, the fat extract would be expected to have the same components (factors) as being instantly claimed because they are indeed the same fat tissue extracts as being claimed as can be appreciated by the extraction method steps taught in the art which are the same as being claimed. Additionally, there was nothing done to the cells to make them have any different function or genetic expression that would make them any different than other cells of the same lineage. The rejection below is included to show that the adipose cells would indeed have the same genetic makeup. It is a mere matter of testing for the specific markers which can be done through an ELISA kit. Thus, the same extraction process would be expected to end up with the same concentration of markers as instantly claimed.
It would have been obvious to persons skilled in the art to use the instantly claimed process for creating a fat extract without other ingredients (also known in the art as nanofat) for the method of promoting proliferation and antiaging of fibroblasts and for the production of collagen. Wang teaches that the secretome of the ADSCs to be useful for collagen production, proliferation and antiaging, and together with Tonnard, Yu and Yunfei, teach the method to obtain the fat extract as instantly claimed. Tonnard teaches wherein the process of emulsifying and filtering the lipoaspirate after obtaining fat particles would also lead to the antiaging effect. Thus the fat extract from Wang and Tonnard’s teaching would appear to be the same as that of the instant invention. Additionally, Yu and Yunfei teach the same method of obtaining the fat extract as claimed. Together the prior art describes the extraction method and the same benefits from the administration of the fat extract and so it appears that the instant methods are the same as that of the combined prior arts. Yu also makes obvious reasons to substitute the method for obtaining the extract in Wang’s disclosure, because Yu teaches use of the cell-free liquid fraction could theoretically avoid the cell-related concerns in clinical applications; these concerns include the genetic stability of cells after processing, cell activity and survival after injection, and the storage of cells for multiple administration, as well as the immunogenicity of cells when using allogeneic fats. Based on these clues, we purified the liquid fraction, namely the “fat extract” (FE), from nanofat using a mechanical approach to remove the cellular components and the lipid remnants. Yu and Wang recognize the therapeutic potential comes from the ADSC’s which are abundantly found in adipose tissues and Yu gives optimal methods for obtaining the cell-free liquid components known to have said therapeutic potential.
Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et. al. (From IDS, Protective effects of adipose-derived stem cells secretome on human dermal fibroblasts from ageing damages, Int J Clin Exp Pathol 2015; 8(12): 15739-15748), Patrick Tonnard et. al. (Nanofat Grafting: Basic Research and Clinical Applications, Plastic and Reconstructive Surgery, Vol 132, No. 4, 1017-1026, October 2013), Nie Yunfei and Zhang Linghua (CN109876189A) hereinafter Yunfei with support from Yu et. al. (Fat extract promotes angiogenesis in a murine model of limb ischemia: a novel cell-free therapeutic strategy, Stem Cell Research and Therapy, 9, 294, 08-Nov-2018) as applied to claims 1-5, 7-10 and 16 above, and further in view of Jennifer Le, Merk Manual (https://www.merckmanuals.com/home/drugs/administration-and-kinetics-of-drugs/drug-administration). This rejection is maintained due to the arguments filed on 12/23/2025.
Wang teaches methods for promoting the proliferation of fibroblasts, promoting the anti-aging of fibroblasts and promoting the production of type 1 collagen by administering a fat extract without added ingredients or a composition or a product containing the fat extract without ingredients to a subject as described above, however is silent on the formulations.
Regarding claims 17-18, Le teaches that drugs are taken into the body by several routes which can be orally, by injection, applied to the skin topically etc. and each route has specific purposes, advantages and disadvantages (see first para.).
Le teaches different formulation types such as tablets, capsules, ointment, cream, lotion, solution, powder, or gels and liquids (see p 1-2).
Therefore it would have been obvious to persons skilled in the art before the effective filing date to create different formulations for the composition taught by Wang in order to allow for different routes of administration. It would have also been obvious to create the formulations with a carrier and/or excipient because these are routinely done and conventional in the art.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et. al. (From IDS, Protective effects of adipose-derived stem cells secretome on human dermal fibroblasts from ageing damages, Int J Clin Exp Pathol 2015; 8(12): 15739-15748), Patrick Tonnard et. al. (Nanofat Grafting: Basic Research and Clinical Applications, Plastic and Reconstructive Surgery, Vol 132, No. 4, 1017-1026, October 2013), Nie Yunfei and Zhang Linghua (CN109876189A) hereinafter Yunfei with support from Yu et. al. (Fat extract promotes angiogenesis in a murine model of limb ischemia: a novel cell-free therapeutic strategy, Stem Cell Research and Therapy, 9, 294, 08-Nov-2018) as applied to claims 1-5, 7-10 and 16 above, and further in view of Chang Lin et. al. (Freeze/thaw induced demulsification of water-in-oil emulsions with loosely packed droplets, Separation and Purification Technology, Vol 56, Issue 2, August 15, 2007). This rejection is maintained due to the arguments filed on 12/23/2025.
Wang teaches methods for promoting the proliferation of fibroblasts, promoting the anti-aging of fibroblasts and promoting the production of type 1 collagen by administering a fat extract without added ingredients or a composition or a product containing the fat extract without ingredients to a subject as described above, however is silent on the step of adding a freeze/thaw treatment before the centrifugation step.
Lin’s general disclosure is an abstract on using freeze/thaw to induce demulsification of water-in-oil emulsions.
Lin teaches “Freeze/thaw treatment has been widely investigated for phase separation of oil-in-water (O/W) emulsions. However, it is a new application for destroying the inverted emulsions, water-in-oil (W/O) emulsions. In this study, freeze/thaw treatment was used to break the W/O emulsions with loosely packed droplets that were produced from the oils generally adopted as membrane phase in emulsion liquid membrane (ELM) process. The effects of emulsion system parameters and freezing conditions on demulsification performance were investigated. A near linear relationship was observed between demulsification performance and water content (30-65%). Demulsification performance greatly increased with the increase of droplet size (2.7-7.3 μm), while it was slightly affected by oil type. Four freezing methods were employed including freezing in refrigerator, cryogenic bath, dry ice and liquid nitrogen. The best freezing method for water removal was freezing in cryogenic or dry ice, and its efficiency was over 70% for all experimental systems with 60% water content regardless of droplet size and oil phase type. Furthermore, microscopic process of demulsification was monitored using optical microscope and the coalescence of droplets was simulated. From the experiments, the gradual demulsification process induced by freeze/thaw was proven and a collision mechanism was proposed. Meanwhile, the volume expansion of water turning to ice and interfacial tension of oil-water interface were determined as main driving forces of demulsification. The proposed mechanism and driving forces can explain the influences of various parameters on demulsification performance well.” (see abstract).
Therefore it would have been obvious to add in a freeze/thaw cycle before instantly claimed step 5 as discussed by Lin et. al. because this process can help to induce demulsification of water-in-oil emulsions with fat droplets. The process of using freeze/thaw as a means for breaking up an emulsion into its constituent components such as oil and water is routinely done in the art and would have been obvious for the reasons just stated.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 7-10, 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16-32 of copending Application No. 18/578698 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are directed to administering the same composition which is obtained from the same method. Although the copending application is directed to a different patient population (treating ovarian insufficiency) the administration of the same components would be expected to have the same effects as instantly claimed which is promoting proliferation of fibroblasts, promoting anti-ageing of fibroblasts and promoting production of collagen I in fibroblasts. Also patient populations exist wherein a person can be in need of both treatments. The extraction methods of the fat are the same (see instant claim 1 and copending claims 27 and 30). The same cell free fat extract obtainable by the same method steps would be expected to have the same fucntions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 12/23/2025 have been fully considered but they are not persuasive. The applicant’s arguments are based on the idea that they believe the Office is arguing that Wang’s teachings which are only directed to adipose-derived stem cell-conditioned media (ADSC-CM) are the same as the instant inventions “fat extract” and is not the same as the lipoaspirate coming from adult adipose tissues. The Office has not made this argument and instead gave a motivational statement as to why one would use the combined art to arrive at the instant invention, by first looking at Wang’s entire disclosure and being able to determine that the active components for promoting proliferation of fibroblasts, anti-aging of fibroblasts and collagen type-1 production do indeed come from the extracts of adipose tissue. As previously stated, Wang teaches “In our group, human dermal fibroblasts (HDFs) at different senescent levels were exposed to UVB then cultured in conditioned medium of ADSCs (ADSC-CM) that contains the whole raw secretome of and takes advantages of easier storage and safer application over ADSCs. Afterwards we detected related biochemical indexes, aiming at more comprehensively observing the ageing characteristics of HDFs as well as evaluating the antiageing effects of ADSCs secretome (see page 15740 second para.). Here Wang teaches that it is the adipose-derived stem cells whole raw secretome that are the active and beneficial components, not necessarily the diluted medium in which the cells are cultured. Wang specifically uses the cultured medium because as noted, it is easier for storage and for safe application purposes. Persons having ordinary skill in the art would recognize that the ADSC’s secretome (what is secreted from inside the cell) are the active components and not necessarily the medium which is a diluted carrier for the active components. The applicant argues that the difference in Wang vs their extract is that theirs is from lipoaspirate and Wang’s is from cultured adipose-derived stem cells. The applicant is not claiming these limitations and therefore Wang’s adipose-derived stem cell secretome would also be relevant to the broadly claimed “fat extract”. Also, Wang indeed teaches starting with human lipoaspirate (see materials and methods, first para.), and although Wang isolates ADSC’s, the teaching that the activities previously described are still recognized as coming from a fat extract are relevant. Clearly ADSC’s are contained in a lipoaspirate or else they would not have been able to be isolated from the fat extract. These activities come from adipose-derived stem cells secretome and they are also found to be existing in the lipoaspirate.
The applicant does not require that the fat extract is a lipoaspirate as they continue to argue. The applicant claims simply a “fat extract” prepared by providing raw fat tissue, shredding, rinsing, centrifuging to obtain layers and so on. Therefore the fat extract is not so limited and even so Wang teaches that the fat tissue is indeed from lipoaspirate. Persons having ordinary skill would recognize this and determine to use the extraction techniques taught by Tonnard, Yu and Yunfei as these pieces of art give detailed descriptions for obtaining the fat extract from the lipoaspirate which is known from Wang’s art for promoting proliferation of human dermal fibroblasts along with anti-aging and collagen production. The applicant argues that the extracts are different but this is not the case. The applicant specifically recognizes this as they recite in their own specifications that “In another preferred embodiment, the cells are selected from the group consisting of endothelial cells, adipose stem cells, macrophages, and stromal cells” (see page 3, lines 3-4). It is the emulsified components of those fat cells that exert the activities as is recognized by both the prior art and the applicant. The method to obtain the adipose secretome is described in multiple pieces of art (Tonnard, Yu and Yunfei) and the activities of that extract is described by Wang. Persons having ordinary skill in the art would recognize that indeed adipose-derived stem cells exist in the lipoaspirate and are collected through the centrifugation steps and discarding of the top and bottom layers
Yu teaches to produce a cell-free extract directly from human fat tissue and evaluate its potential therapeutic efficacy and describes similar ways for obtaining the extract as claimed.
Yu also teaches “Adipose tissue has currently gained significant importance since it serves as an abundant source of ADSCs. As a result, adipose tissue and its derivatives, initially used for soft tissue augmentation, have now been used for regenerative purposes. For example, the autologous fat graft has been used to successfully treat irradiated tissue and chronic ischemia [13–17]. The stromal vascular fraction (SVF), a mixed cell population commonly isolated by the enzymatic digestion of fat, has been used in therapies for burn injury and diabetes [18, 19]. More recently, nanofat, a fat emulsion produced through mechanical forces, has been shown to improve fat graft survival and skin rejuvenation and has been used in the treatment of atrophic scars, among other conditions [20–25]. The regenerative effects of the aforementioned materials are considered mainly related to their cellular component via the secretion of growth factors”. Here Yu clearly teaches that it is the ADSC’s which are abundantly found in adipose tissue which comprise the fat extract.
The applicant is arguing that it is the ADSC-CM of Wang’s teaching that the Office relies upon to compare to the instant invention. This is clearly not the only piece of art relied upon. The Office relies on Yu to show there are more optimal ways of obtaining the cell-free fat extract which comprises of the ADSC’s in Wang’s disclosure. The activity of the ADSC’s secretome is described in Wang but a more optimal way for obtaining the active extract is taught by Yu (and Tonnard and Yunfei) and clear reasons to modify the method are also discussed by Yu and in the above motivational statement.
The applicant compares the fat extract obtained by the instantly claimed method (also taught in the prior art) to that of Wang’s ADSC-CM and shows that there is some unexpected effect because the fat extract shows a much-improved effect when compared to the ADSC-CM of Wang. This effect is completely expected and because Wang teaches that the reason the cultured media was used was for easier storage purposes and as explained before persons having ordinary skill in the art would recognize that the ADSC cultured media would be a diluted version of the extracted components of those ADSC’s. So it would be expected that the fat extract would exert an overall greater effect.
The applicant argues that stem cells are responsible for the effects taught by Tonnard but the Office is not merely relying on Tonnard’s art alone. Yu teaches reasons to not include cells in the final composition that would be administered.
The applicant argues that those skilled in the art would recognize that ADSCs are the rarest and most therapeutically active in adipose tissue and so how could persons having ordinary skill in the art assume that a cell-free fat extract predominantly composed of mature adipocytes to have the same activity? Yu teaches that ADSC’s are indeed abundant in fat tissues and teaches methods for obtaining the cell-free fat extract. Persons having ordinary skill would simply have to read Yu to learn that one can expect that the growth factors and active components are still to be expected in the cell-free fat extract.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 BOECKELMAN Examiner, Art Unit 1655
/ANAND U DESAI/ Supervisory Patent Examiner, Art Unit 1655