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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/04/2026 has been entered.
Response to Amendment
Applicant's amendment and argument filed 05/04/2026, in response to the final rejection, are acknowledged and have been fully considered. Any previous rejection or objection not mentioned herein is withdrawn.
Claims 1-8, 10-11 and 13-14 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 1-8, 10-11 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Graham Vesey (From IDS, US20110293577A1) and Yunfie (CN109876189A), with supporting evidence from Ziyou 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 amendments filed on 5/04/2026.
Regarding claims 1-3 and 6, Vesy discloses “a method of treating an inflammatory disorder or a cartilage or bone disorder, or alleviating pain associated with an inflammatory disorder in a subject, comprising administering to the subject a pharmaceutical composition which comprises: (i) an adipose tissue-derived cell suspension which comprises adipocytes; or (ii) a cell-free extract which is prepared from an adipose tissue-derived cell suspension,” (see abstract).
Vesy teaches that “in a further embodiment the cell suspension is not suspended in a medium, but instead the cells are suspended in liquid which is formed during the dissociation of the tissue” (see 0046).
Vesy discloses “In certain embodiments the cartilage or bone disorder is a cartilage or bone fracture, for instance a non-union bone fracture, or osteoporosis” (see 0016) and wherein the composition is administered for a cartilage or bone disorder which may include a loss of bone or cartilage volume and strength (see 00825).
Regarding claim 10, Vesy teaches the composition to have a pharmaceutically acceptable carrier (see 0083).
Regarding claim 11, Vesy discloses topical administration and subcutaneous injection (see 0070).
Regarding claim 14, Vesy teaches systemic administration may involve intravenous administration of the pharmaceutical composition (see 0073).
Vesy does not teach the instantly disclosed method for obtaining the cell-free fat extract.
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). Yunfei also teaches rinsing the tissue with saline (see S5 and S6 of claim 1).
Yunfei teaches that this method recycles high speed centrifugation to remove the cell component and ECM, and cell factor loss is low (see abstract).
Regarding claims 6-8, the same extraction process would inherently bring about the same components in the extract as claimed. As additional evidence Yu, discloses these same extracted components.
Yu’s disclosure is relied upon to show that a fat tissue extract would contain the same components as claimed.
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). These appear to be within ranges of what is instantly claimed as can be appreciated from the values of those components in Yu’s Figure 4.
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 biomarkers present and within similar amounts as this appears to be inherent to the fat extract itself.
It would have been obvious to persons having ordinary skill in the art to adopt Yungfei’s or Yu’s methods in mechanically separating adipose tissue by first providing fat tissue and crushing 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 Yunfei or Yu to appreciate the order of operations and to see which layers need to be held and discarded (top and bottom layers). Yunfei and Yu both also teach to emulsify and centrifuging after separation, and it would have been obvious to persons skilled in the art to filter and de-bacterizing the fat extract in order to not administer a sample containing bacteria. Also Yu teaches sterilizing which would be the same as de-bacterizing.
Persons having skill in the art would look to Yu or Yunfei for an improved method of obtaining a cell-free fat extract for the composition taught by Vesy, because as Yunfei teaches it can recycle high speed centrifugation to remove the cell component and cell factor loss is low.
The method for obtaining the cell-free fat extract is known in the art and the use of the cell-free fat extract for treating osteoporosis has also been taught, thus using this extract for disuse osteoporosis or for a bone which is selected from the list of bones in instant claim 4, would have been prima facie obvious given the prior art.
There would have been a reasonable expectation of success in arriving at the instant invention given that the prior art already teaches and makes obvious each element of the invention.
Response to Arguments
Applicant's arguments filed 05/04/2026 have been fully considered but they are not persuasive. The applicant argues that there cannot be an argument of inherency from the Office because they believe the invention is distinct over the prior art in that Vesey’s invention is directed to adipocyte cell cultures or rather a fraction of the culture medium in which the active adipocyte secretome was secreted as opposed to the inventors claimed adipocyte secretome which includes selectively secreted proteins, factors and exosomes. The applicant amended their claims to recite a limitation which were to exclude any additives being included with the cell-free fat extract. The applicant believes that since Vesey describes in two examples (examples 3 and 4) a formulation which is the adipocyte fat free extract along with DMEM that the this is the only embodiment which can be argued against. Vesey also teaches such exclusion of the DMEM because Vesey states “in a further embodiment the cell suspension is not suspended in a medium, but instead the cells are suspended in liquid which is formed during the dissociation of the tissue”. This would be the adipocyte secretome (extract).
The applicant argues that an inherency argument cannot be made because they have merely argued against an embodiment that includes DMEM. Vesey does not merely teach one embodiment. Vesey teaches the same adipocyte cell-free secretome and Yunfei or Yu each teach the exact same method to obtain the extract. The applicant’s invention is the same and the only difference that has been argued is the presence of DMEM which Vesey does not require. Therefore inherency would naturally flow from the same administration of the same components which were extracted in the same way would ultimately have the same effect even if it was not known at the time of filing. Furthermore, It is well established that “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.” In re Baxter Travenol Labs, 21 USPQ2d 1281, 1285 (Fed. Cir. 1991). In Baxter, the court held that even when the prior art did not expressly disclose hemolysis-suppression feature or property of a blood bag plasticizer, such unrecognized feature or property is insufficient for rebutting a prima facie case of obviousness over a prior art blood bag that utilized the same plasticizer. Id. See also Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Int. 1985) (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious’). Something which is old does not become patentable upon the discovery of a new property."[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). The art already recognizes the same patient population of administering the composition to patients having a bone disorder which may include a loss of bone.
The applicant argues that the preparation methods and sources of active ingredients are clearly distinct because they think that examples 3 and 4 of Vesey teach entirely different inventions, however they are not distinct as argued because Vesey teaches exclusion of the media.
The applicant argues that since the applicant was the first to discover the properties (i) increasing bone volume fraction; (ii) increasing trabecular bone number; (iii) increasing trabecular bone junction density; (iv) increasing bone mineral density; (v) increasing trabecular thickness; and/or (vi) decreasing trabecular separation of a subject with osteoporosis, that the advantages are unexpected and would not be obvious over the prior art. The discovery of a mechanism of action or latent property does not make the instant application patentably distinct over the prior art. The art recognizes administering the composition to persons having bone loss and specifically bone volume. Increasing trabecular bone number, increasing trabecular bone junction density, increasing bone mineral density, and increasing trabecular thickness are ways of increasing bone volume and would have been expected and obvious.
Conclusion
Currently no claims are allowed.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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