DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 29 January 2026. Claim 1 has been amended. Claims 2 and 3 have been cancelled. Claims 8-12 remain withdrawn. Claims 1, 4, 6, and 7 are currently pending and under examination.
This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/KR2021/013900, filed October 8, 2021, which claims benefit of priority to Korean Patent Application No. 10-2020-0130138, filed October 8, 2020.
Withdrawal of Rejections:
The rejection of claims 1-4, 6, and 7 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn.
The rejection of claim 3 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn.
Maintenance/Modification of Rejections Necessitated by Amendment:
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, 4, 6, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Osteoblastic differentiation of rabbit mesenchymal stem cells loaded in a carrier system of Pluronic F127 and Interpore, Chang Gung Medical Journal, Vol. 29, No. 4, (2006), pp. 363-372 – Previously presented), in view of Chung (US 2017/0216416; Published 2017 – Previously presented).
With regard to claim 1, Huang et al. teach a method of differentiating mesenchymal stem cells (MSCs) into osteoblasts (Title, Abs.). The method comprising mixing MSCs at a cellular concentration of 2x106 into Pluronic® F-127 (poloxamer 107) surfactant; placing Interpore, which is a commercial porous scaffold, in the wells of a 24-well plate, and injecting the surfactant/MSC mixture onto the porous scaffold (p. 365, Left col., Hydrogel and mesenchymal stem cells, para. 1-2; p. 364, Left col., last para.; p. 366; Left col., Loading of interpore with MSCs/hydrogel, para. 1 to Right col., line 1).
The Pluronic® F-127 provides a hydrogel that encapsulates the MSCs (p. 364, Left col., last line to Right col., line 2). It is noted that Applicant does not specifically define the term “bubble.” Thus, encapsulation of the MSCs is deemed to be inoculating the MSCs into a poloxamer “bubble.” The Interpore scaffold is an air-permeable membrane and the Pluronic® F-127 is a poloxamer. Thus, when the Interpore scaffold is coated with the Pluronic® F-127 polymeric surfactant, it creates an air-permeable polymer membrane with surfactant bubbles encapsulating the MSCs.
This claim includes a limitation of producing the poloxamer bubbles by the claimed process. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Here, the MSCs of Huang et al. are encapsulated into a poloxamer hydrogel, which is deemed to be a poloxamer “bubble.” The poloxamer hydrogel is used for the same purpose as claimed: to encapsulate the MSCs and support differentiation of the MSCs into osteoblasts. Functionally, poloxamer hydrogel encapsulation bubble of Huang et al. is the same as the claimed bubble. Therefore, the poloxamer hydrogel encapsulation bubble of Huang et al. is the same as, or would have rendered obvious, the poloxamer bubble produced by the claimed process.
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"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983).
After providing the air-permeable polymer membrane with surfactant bubbles encapsulating the MSCs, osteogenic medium is added to each well to provide for osteogenic differentiation of the MSCs into osteoblasts (p. 365, Left col., Hydrogel and mesenchymal stem cells, para. 1-2).
MSCs at a cellular concentration of 2x106 are inoculated into the surfactant, and the mixture injected into a 24-well plate (p. 365, Left col., Hydrogel and mesenchymal stem cells, para. 1-2), which provides about 8.3x104 cells per well plate. While it is not specifically taught that the MSCs are inoculated into the surfactant at a density of 1 x 103 to 1 x 105 cells/cm2, it would have been routine for an ordinary artisan to determine the appropriate cell density based on the specific materials being used to perform the method. Additionally, please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the density of the MSCs inoculated into the surfactant to result in the presence of a desired amount of osteoblasts differentiated from the MSCs when practicing the method of Huang et al.
While Huang et al. teach obtaining osteoblasts from MSCs, it is not specifically taught that the osteoblasts are isolated.
Chung teaches a method for differentiating stem cells, including MSCs, into osteoblasts (Abs.), the method including differentiating the stem cells into osteoblasts and isolating the produced osteoblasts (Para. 159).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Huang et al. with Chung, because both teach methods for differentiating stem cells, including MSCs, into osteoblasts. The isolation of produced osteoblasts after their differentiation from stem cells is known in the art as taught by Chung. The isolation of the osteoblasts as taught by Chung in the method of Huang et al. amounts to the simple substitution of one end step for another, and would have been expected to predictably and successfully provide an alternative end use for the osteoblasts produced by the method of Huang et al.
With regard to claim 4, Huang et al. teach that the MSCs are derived from bone marrow (Abs.).
With regard to claims 6 and 7, taken together, Huang et al. and Chung render obvious the method as claimed, including the components as claimed. As such, the results that the osteoblasts have higher expression levels of connexin 43 (CX43), Runt-related transcription factor 2 (RUNX2) and collagen type lAl (COL1A1) than undifferentiated stem cells and mature osteocytes; higher expression levels of angiopoietin 1 (ANGPT1) and alkaline phosphatase (AP) than undifferentiated stem cells; lower expression levels of osterix (OSX), osteocalcin (OCN) and osteopontin (OPN) than mature osteocytes; and lower expression level of Ki-67 than undifferentiated stem cells, would naturally flow from performance of the method as rendered obvious by Huang et al. and Chung.
Response to Arguments
Applicant urges that Huang et al. do not teach or render obvious the poloxamer bubbles, including being produced by the method, as claimed. Instead, Huang et al. discloses a thermo-responsive bulk hydrogel that undergoes sol-gel transition depending on temperature, while the present invention includes a mechanically induced bubble forming process that creates a gas-liquid interfacial structure.
Applicant’s arguments have been fully considered, but have not been found persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that the bubble is a gas-liquid interfacial structure) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As discussed in the modified rejection above, Applicant does not specifically define the term “bubble.” The Pluronic® F-127 provides a hydrogel that encapsulates the MSCs (p. 364, Left col., last line to Right col., line 2), wherein encapsulation of the MSCs is deemed to be inoculating the MSCs into a poloxamer “bubble.”
With regard to Applicant’s argument that Huang et al. do not teach production of the bubble as now claimed, it noted that this is a product-by-process limitation as discussed in the modified rejection above. The MSCs of Huang et al. are encapsulated into a poloxamer hydrogel, which is deemed to be a poloxamer “bubble.” The poloxamer hydrogel is used for the same purpose as claimed: to encapsulate the MSCs and support differentiation of the MSCs into osteoblasts. Functionally, poloxamer hydrogel encapsulation bubble of Huang et al. is the same as the claimed bubble. Therefore, the poloxamer hydrogel encapsulation bubble of Huang et al. is the same as, or would have rendered obvious, the poloxamer bubble produced by the claimed process.
Conclusion
No claims are allowable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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