Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 05 December 2025.
CLAIMS UNDER EXAMINATION
Claims 5-9 and 11-13 have been examined on their merits.
PRIORITY
The Applicant claims priority to KR10-2018-0150057 filed on 28 November 2018.
WITHDRAWN REJECTIONS
The rejection of claims 5-9 and 11-13 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph has been withdrawn due to claim amendment.
NEW REJECTIONS
Claim 5 has been amended to require adipose tissue obtained from liposuction. The claim has been amended to recite pressurizing carbon dioxide at 300 to 600 bar.
New grounds of rejection have been necessitated by claim amendment.
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, 7 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (previously cited; Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue. Materials Science and Engineering C 75 (2017) 349–358) in view of Lee et al. (previously cited; Lipid-free scaffolds for human volume replacement or cell culture and use thereof. US20100178681),
Vaquero et al. (previously cited; Extraction of fat from pigskin with supercritical carbon dioxide. J. of Supercritical Fluids 37 (2006) 142-150) and James et al. (previously cited; Systems and Methods For Supercritical Chromatography. US2017/0189831 06 July 2017).
Wang teaches a method for delipidation and decellularization of adipose tissue
using supercritical carbon dioxide (SC-CO2) (Abstract). Wang teaches an extracellular matrix (ECM) is produced (Abstract). Wang teaches adipose tissue is a rich source of extracellular matrix (ECM) (Abstract). The method produces an ECM material with preserved key proteins, including collagen, elastin, fibronectin and laminin (Abstract).
Wang obtains a lipoaspirate tissue (hence, obtained by liposuction) from patients (see 2.1 of Materials section). Wang teaches a lipoaspirate is adipose tissue (page 350, left column, second paragraph). The adipose tissue is rinsed (i.e., washed) with distilled water in order to completely remove blood components (see 2.2 of Materials section). The tissue is then loaded into the reaction vessel with ethanol as modifier. Liquid carbon dioxide (CO2) was then flowed into the reaction vessel in the direction of the pointed arrows in Figure 1. CO2 was first compressed by a pump and then passed through the regulator until the desired pressure (180 bar) was achieved. Wang teaches the supercritical temperature can be achieved at 30.85°C (see page 353, left column, second paragraph). The temperature of the reaction vessel was maintained at 37 °C for 3 h. (see 2.2 of Materials section).
Figure 1 discloses a CO2 gas cylinder. Figure 1 discloses the modifier (ethanol) is in a vessel on one side of the carbon dioxide cylinder. As set forth above, the art teaches the CO2 was compressed to achieve the desired pressure. Figure 1 discloses the supercritical fluid and ethanol (co-solvent) are combined. Figure 1 discloses fluid (hence, solvent) is moved out of the reactor containing the adipose tissue, ethanol and supercritical CO2. The art teaches the ECM is collected (recovered) (see page 350, right column, last sentence of first paragraph).
The teachings and deficiencies of Wang are as follows:
Wang teaches washing an adipose tissue obtained from a liposuction, but does not teach mincing or centrifuging the adipose tissue.
Wang pressurizes CO2 to obtain a supercritical fluid, but does not teach a pressure of 300 to 600 bar.
Wang teaches a carbon dioxide cylinder and a co-solvent, but does not teach mixing a co-solvent discharged from a co-solvent chamber with the pressurized supercritical fluid.
Wang does not explicitly teach preheating.
Wang does not teach the claimed reaction temperature.
Wang does not teach the claimed flow rate.
Lee et al. teach a method of processing adipose tissue to remove lipids (Abstract). The art teaches fat tissue contains extracellular matrix ([0039]). Adipose tissue is pulverized and sonicated (Abstract; [0043]). The tissue is fragmented (hence, minced) to isolate lipids by ultrasonic treatment (Abstract). Lee teaches washing and centrifugation ([0032]).
Vaquero identifies the optimum process conditions for extracting adipose tissue using SC-CO2 as a solvent (Abstract; page143, left column, first paragraph).
Vaquero teaches CO2 is supercritical at temperatures above 31°C (see page 142, right column, first paragraph). The maximum temperature assayed was 40 °C since collagen may experience denaturational transitions under higher temperatures (see section 3.1.1 on page 144). Figure 5 analyzed fat removal increases as a function of pressure. The art analyzes pressures between 300 and 600 bar. Because the art teaches different pressures are used, CO2 is pressurized when it leaves the cylinder.
Figure 5 illustrates fat removal is highest at pressures between 300-600 bars when CO2 is at a supercritical temperature (40°C) compared to a non-supercritical temperature (20°C; see section 3.2.1 on page 145). Figure 11 discloses the effect of flow rate (5-20kg CO2/hour) on fat removal. The art teaches extraction efficiency increases with flow rate (see page 148, section 3.3.3).
Vaquero also teaches the following:
Pigksin is obtained from an animal and cut into pieces, identified as “minced skin” (page 143, left column, second paragraph of section 2.1). Vaquero teaches the skin contains fat and water (see section 2.1, first paragraph). Vaquero teaches water is removed (see section 3.2.3). Pigskin is placed in the extractor (page 143, right column, third paragraph of section 2.3). Figure 1 discloses a CO2 container shaped like a cylinder. CO2 Solvent is circulated through the extractor (same cited section). Therefore solvent is withdrawn from the reactor. Because the art illustrates the reactor has sides (Figure 1), the solvent must be withdrawn through a side of the reactor.
James et al. teach a system for supercritical fluid chromatography (Abstract). James teaches a CO2 bottle (cylinder) and a co-solvent in a co-solvent vessel (see Figure 1; [0033] [0050] [0166]). The art teaches the co-solvent is an organic, polar solvent that aids in separation ([0004] [0174]). CO2 leaving the supply tank flows through a pre heater ([0155]). James teaches doing so bring the temperature up to operation temperature ([0155]). The art teaches the supercritical CO2 and co-solvent flow through a static mixer that ensures homogenous mixing (see Figure 1; [0155]). James teaches a flow rate of at least about 10 ml/min , e.g., at least about 15 ml /min , 20 ml / min , 25 ml / min , 30 ml / min , 35 ml / min , 40 ml /min , 45 ml /min , or 50 ml / min, to about 300 ml / min (column 8, lines 40-43).
It would have been obvious to mince and centrifuge the adipose taught by Wang. Wang teaches removing lipids and cells from adipose tissue. One would have been motivated to mince and centrifuge adipose tissue since Lee teaches doing so to remove
lipids and cells. One would have had a reasonable expectation of success since Lee teaches adipose tissue can be decellularized and delipidated using these steps. One would have expected similar results since Wang and Lee are both directed to methods of processing adipose tissue.
It would have been obvious to try reacting the supercritical CO2 taught by Wang at a temperature between 30-32°C. Wang reacts supercritical CO2 at 37°C, but teaches supercritical conditions can be achieved at 30.85°C (between 30-32°C). Vaquero teaches adipose extraction is a function of temperature. The skilled artisan would optimize the temperature to obtain the desired level of extraction. MPEP 2144.05. One would have had a reasonable expectation of success since Wang teaches supercritical conditions can be obtained at 30.85°C. One would have expected similar results since Wang and Vaquero are both directed to adipose extraction using supercritical CO2.
It would have been obvious to pressurize CO2 at 300 to 600 bar. Wang pressurizes CO2 to obtain a supercritical fluid and Vaquero teaches supercritical CO2 is prepared using 300 to 600 bar pressure. Vaquero teaches extraction of adipose tissue increases as a function of pressure. The skilled artisan would optimize the pressure to obtain the desired level of extraction. One would have had a reasonable expectation of success since Vaquero teaches supercritical CO2 can be obtained at 300-600 bars. One would have expected similar results since Wang and Vaquero are both directed to adipose extraction using supercritical CO2.
It would have been obvious introduce solvent to a reactor at a flow rate of 18 to 70 ml/min. Wang adds supercritical CO2 to a reactor to separate an adipose tissue sample and James teaches supercritical CO2 can be added to a reactor at 20 ml/min to 50 ml/min for sample separation. The skilled artisan would optimize the flow rate since Vaquero teaches fat extraction efficiency is a function of flow rate. One would optimize the flow rate to obtain the desired level of extraction. One would have had a reasonable expectation of success since James teaches flow rates between 18 to 70 ml/min can be used for extraction by supercritical CO2. One would have expected similar results since Wang, Vaquero and James are directed to methods of using supercritical carbon dioxide for sample separation.
It would have been obvious to mix a co-solvent discharged from a co-solvent chamber with the pressurized supercritical fluid. Wang mixes solvent CO2 with a co-solvent for extraction. James teaches mixing supercritical carbon dioxide with a co-solvent stored in a co-solvent vessel in a method of sample separation. One would have had a reasonable expectation of success since James teaches co-solvents and supercritical carbon dioxide stored in separate containers can be mixed. One would have expected similar results since both references use supercritical carbon dioxide for sample separation.
It would have been obvious to combine the teachings of the prior art by preheating the solvent taught by Wang. One would have been motivated to do so to bring the liquid up to operating temperature, as taught by James. One would have had a reasonable expectation of success since James teaches solvents used for extraction can be preheated with a preheater. One would have expected similar results since both references use supercritical carbon dioxide for sample separation. Therefore claim 5 is rendered obvious.
Lee teaches tissue discarded after extracted from an obese patient was fragmented and subjected to sonication (110W) 10 to 15 times at 60 to 80° for 10 minutes in distilled water to isolate lipids. The isolated lipids and fat tissue, from which lipids were not isolated, were filtered or centrifuged at 3500 rpm for 5 minutes, followed by washing with 70% ethanol and distilled water, respectively. See Example 1 [0054]-[0056].
It would have been obvious to combine the teachings of the prior art by performing ultrasonication. Wang pretreats adipose tissue and Lee treats washed adipose tissue to ultrasonication. One would do so to remove lipids from the tissue, as taught by Lee.
While Lee teaches sonication at 100 W for 10 minutes, one would optimize the wattage and treatment time to achieve the desired amount of processing. One would have had a reasonable expectation of success using sonication since Lee teaches adipose tissue can be sonicated. One would have expected similar results since both references are directed to methods of processing adipose tissue. Therefore claim 7 is included in this rejection.
Vaquero teaches reaction times up to 200 minutes (3.3 hours; see Figure 3). Therefore claim 11 is included in this rejection.
James teaches the use of ethanol as a co-solvent ([0033]). Therefore claim 12 is included in this rejection.
Wang does not teach the amount of co-solvent recited in claim 13.
James teaches the co-solvent may comprise up to about 20 % v/v of the fluid being pumped through the system (column 15, lines 58-59).
It would have been obvious to use 20 % v/v co-solvent. One would have been motivated to do so since James teaches the co- solvent may comprise up to about 20 % v/v of the fluid being pumped through the system. One would have had a reasonable expectation of success since James teaches co-solvent can be used in this amount for supercritical fluid extraction. One would have expected similar results since Wang and James are both directed to methods of supercritical fluid extraction using ethanol co-solvents. Therefore claim 13 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Wang in view of Vaquero, Lee and James as applied to claim 5 above, and further in view of Nahas et al. (previously cited; Compositions And Methods For Implantation Of Processed Adipose Tissue And Processed Adipose Tissue Products. 2012/0189588 2012).
Claim 5 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. Wang teaches rinsing (washing) adipose tissue with distilled water to remove blood components (see page 350, left column, last paragraph).
Wang does not teach the washing steps recited in claim 6.
Nahas teaches compositions and methods for preparation of processed adipose tissue (Abstract). The invention provides methods for decellularizing the adipose or extracting lipid from the adipose including contacting the adipose with supercritical CO2 ([0025]).
Preparation of the acellular adipose biocompatible biomaterial can be accomplished by performance of homogenization and serial washes in sterile saline or buffers for neutralization, preferably followed by serial washes in a solution to further extract the lipid from the cells ([0137]).
Nahas teaches subcutaneous fat was isolated from the sample by scraping. The scraped adipose tissue was homogenized in a blender. The homogenate was then placed on a strainer and washed for 5 minutes under deionized water to wash lipid and cellular debris. This was repeated three times ([0207]).
It would have been obvious to wash the adipose tissue taught by Wang with deionized water. One would use deionized water to remove lipid and cellular debris as taught by Nahas. While Nahas tissue teaches washing for 5 minutes, one would optimize the time to further clean the adipose tissue. One would do so to completely clean the tissue. One would have had a reasonable expectation of success since Nahas teaches adipose tissue can be washed with deionized water three times. One would have expected similar results since Wang and Nahas are both directed to methods of pretreating adipose tissue. Therefore claim 6 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Wang in view of Vaquero, Lee and James as applied to claim 7 above, and further in view of
Leach et al. (Decellularized extracellular matrix. 2014/0023723).
Claim 7 is rejected on the grounds set forth above. The teachings of the art are reiterated.
Lee teaches ultrasonication at 60 to 80° C. The art is silent regarding lower temperatures for sonication.
Leach discloses a decellularized extracellular matrix. Said matrix can be adipogenic ([0008]). The art teaches sonication ([0013] [0102]). Sonication can be performed on ice to homogenize matrix ([0253]). Ice is interpreted to be a chiller.
It would have been obvious to try performing the sonication step taught by Lee using a lower temperatures. Lee teaches a method of tissue sonication and Leach teaches sonication can be performed using a chiller. While Leach does not explicitly teach a chiller between 2 to 5°C, the ice taught by Leach would be able to reach the claimed temperature. One would have had a reasonable expectation of success since Leach teaches sonication can be performed with chilling. One would have expected similar results since both references are directed to methods of processing adipose tissue. See MPEP 2144.05. Therefore the temperature recited in claim 8 is rendered obvious.
Therefore Applicant’s invention is rendered obvious as claimed.
Claims 9 is rejected under 35 U.S.C. 103 as being unpatentable over Wang in view of Vaquero, Lee and James as applied to claim 5 above, and further in view of Badylak (previously cited; Decellularized Adipose Cell Growth Scaffold. US2018/0125897 10 May 2018).
Claim 5 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. Wang pretreats adipose tissue for extraction. Wang teaches washing adipose tissue. Lee pretreats adipose tissue using washing and centrifugation. Lee teaches centrifugation can be performed at 3500 rpm for 5 minutes ([0056]). The art does not teach the centrifugation conditions recited in claim 9.
Badylak produces an ECM product from adipose tissue ([0010]). The method comprises removing lipophilic constituents from a decellularized scaffold prepared from adipose tissue ([0010]). Badylak teaches samples of adipose ECM can be minced, added to an extraction buffer at 4° C and centrifuged at 3000 g (4941 rpm) for 30 minutes ([0065]).
It would have been obvious to combine the teachings of the prior art by performing centrifugation between 4971 rpm at 4° C. One would have been motivated to do so since Lee teaches a method of processing adipose tissue and Badylak teaches adipose tissue can be process by centrifuging at 4971 rpm at 4° C. It would have been obvious to increase the centrifugation time since Badylak teaches longer centrifugations can be used to process adipose tissue. One would have had a reasonable expectation of success since Badylak teaches adipose tissue can be processed using these conditions. One would have expected similar results since Lee and Badylak are directed to methods of processing adipose tissue. Therefore the temperature recited in claim 9 is rendered obvious.
Therefore Applicant’s invention is rendered obvious as claimed.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 05 December 2025 are acknowledged. The Applicant argues Vaquero does not recognize any ethical purpose to preserve useful proteins in liposuctioned adipose tissue.
In response: Wang extracts ECM from adipose tissue. Wang teaches a lipoaspirate. Therefore the art teaches adipose from liposuction. Wang recovers ECM. Wang teaches key ECM proteins are preserved (Abstract). Therefore the arguments are not persuasive.
The arguments state Vaquero compares fat removal at 20°C and 40°C and teaches fat removal is improved at the higher temperature, while also teaching collagen may be denatured at temperatures higher than 40°C. The Applicant argues the instant specification discloses at temperatures of 35°C or above certain proteins could be denatured to decrease yield of useful proteins. The arguments state in the claimed method, extraction conditions of the supercritical fluid are precisely controlled to a pressure “of at least 300 bar and a temperature of no more than 32°C” to achieve a marked improvement in decellularization and delipidation efficiency as well as in the yield of useful proteins.
In response: Wang teaches supercritical CO2 can be obtained at 30.85 (between 30-32°C). Vaquero teaches adipose extraction is a function of temperature. The skilled artisan would optimize the temperature to obtain the desired level of extraction. MPEP 2144.05. One would have had a reasonable expectation of success since Wang teaches supercritical CO2 can be maintained at 30.85°C. One would have expected similar results since Wang and Vaquero are both directed to adipose extraction using supercritical CO2. Vaquero analyzes pressures between 300 and 600 bar. This reads on the claimed pressure. Therefore the arguments are not persuasive.
Regarding James: The Applicant argues James is directed to chromatography using a different device. The Applicant argues James is directed to separating mixed components from each other, while the claimed extraction method is directed to preserving ECM and useful bioactive components in adipose tissue.
In response: Wang teaches a CO2 cylinder. Wang teaches mixing CO2 and a cosolvent. James is relied upon because it teaches a carbon dioxide cylinder and a co-solvent chamber. While the Applicant argues James is directed to separating mixed components, claim 5 is directed to a method of separating adipose tissue. The method requires separation of water and lipids. Therefore the arguments are not persuasive.
The Applicant states the rejection is based on improper hindsight reasoning. The arguments state there is no motivation to combine the cited references with a reasonable expectation of success.
In response: The rejection is based on the teachings of the prior art. Wang obtains from liposuction. Wang extracts ECM from adipose using supercritical CO2 and a co-solvent.
Vaquero teaches the claimed pressure, and teaches CO2 must be reacted at a temperature above 31°C to be supercritical. Lee is relied upon because it teaches a method of processing adipose tissue to remove lipids. James is relied upon because it teaches using a cosolvent with supercritical CO2. James teaches the co-solvent is an organic, polar solvent that aids in separation. The rejection only relies on teachings of the prior art, and does not include knowledge only gleaned from the specification. See MPEP 2145 XA. Therefore the arguments are not persuasive.
CONCLUSION
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653