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 .
Claims 9-11, and 16 have been amended. Claims 1-16 are pending in the instant application. Claims 1-8 remain withdrawn. Claims 9-16 are under examination on the merits.
Response to Amendment
The Amendment by Applicant’s representative Dr. Keisha Hylton-Rodic filed 06/09/2026 has been entered.
Response to Arguments/Amendments
Claim rejection under 35 U.S.C.§102(a)(1)
Applicant’s amendment of claim 9 by further including the step “separating the buoyant hollow particles with the mammalian cells attached from the media” overcomes the rejection because cited the `377 patent does not specifically disclose the step. The rejection is hereby withdrawn.
Claim rejection under 35 U.S.C.§103(a)
Applicant amended claim 9 by further including the step “separating the buoyant hollow particles with the mammalian cells attached from the media”. In addition, Applicant argued that the Office has not shown that the cited references (i.e., '377, Cell Culturem and Falipou), taken individually or in combination, discloses or suggests the invention of claims 9-15, and neither Cell Culture nor Falipou teach or suggest a method for culturing cells, said method comprising particles that are less dense than a media and separating the buoyant hollow particles with the mammalian cells attached from the media, as disclosed in independent claim 9. Applicant’s amendment and argent have been fully considered, but are not sufficient to overcome the rejection further in view the new prior art Weigun et al., Journal of Chromatography A, (2016), v.1466, p.29-36, necessitated by the amendment. The rejection is maintained and revised.
Claim Rejections - 35 USC § 103 (revised)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 9-16 are rejected under 35 U.S.C. 103 as being unpatentable over GB2112377B (“the `377 patent”) to Downs et al. in view of Fundamental Techniques in Cell Culture, Lab Handbook, 4th Ed., (2018), Millipore Sigma (“Cell Culture”), Falipou et al., Sensors and Actuators, (1999), v.74, p.81-85, and Weigun et al., Journal of Chromatography A, (2016), v.1466, p.29-36.
In terms of claims 9-11, the `377 patent does not specifically disclose the buoyant hollow particles are less dense than a media. Instead, the `377 patent (claim 4) discloses the spherical shells have an average density substantially equal to said predetermined density such that said microcarrier is buoyantly suspended in said medium. The '377 patent discloses spherical shells of silicate glass with a density substantially equal to the predetermined density of the cell culture media, such that the microcarriers may be suspended in said medium. See e.g., '377, page 3, lines 1-15. One ordinary skilled in the art would have known that in order to make microcarriers to be suspended in a medium, the density of the microcarriers should be equal or less than the media, which is consistent with the term “a density substantially equal to the predetermined density of the cell culture media”. Furthermore, the `377 patent (claim 4) and present claim 9 are both drawn to a method for culturing cells using buoyant hollow particles.
The `377 patent (claim 4) discloses a method of growing anchorage-dependent cells using microcarriers in a cell culture medium of predetermined density, in which the microcarriers are comprised of spherical shells of essentially homogenous silicate glass composition and have an average density substantially equal to said predetermined density such that said microcarrier is buoyantly suspended in said medium. In addition, the `377 patent (claim 5) discloses the microcarriers comprises a multiplicity of hollow spherical shells of essentially isotropic silicate glass composition. The `377 patent (Abstract, p. 1, lns. 6-12, and p. 4, lns. 23-26) discloses hollow glass shell microcarrier for growth of cell cultures. The `377 patent (page 8) discloses the cultured cells are mammalian cells of human foreskin fibroblast cultured in DMEM media with 5% fetal bovine serum, and murine fibro-sarcoma and Walker carcinosarcoma in RPMI media with 10% fetal calf serum. The '377 patent (p.3, lns. 4-7) specifically teaches “The microcarrier shells are substantially buoyant in the culture medium and may be readily maintained in suspended state by mild agitation, such as by mild aeration using carbon dioxide bubbles which are otherwise useful to control medium pH”.
In terms of the limitation “separating the buoyant hollow particles with the mammalian cells attached from the media”, it is also taught and/or suggested by the `377 patent because the prior art teaches using microcarriers for growing anchorage-dependent mammalian cells in a cell culture medium. It is well-understood that the obtained anchorage-dependent mammalian cells must be separated from the medium after cell culture, according to the passaging cells procedure of “cell culture” described in Wikipedia. In addition, separating buoyant hollow particles with the mammalian cells attached from the media is a common experimental procedure, which is well-known to one ordinary skilled in the art such as through centrifugation and resuspension as being described by Weigun et al. in Fig. 1 at p. 30, and “2.4. Capture of Cryptosporidium parvum oocycts” at p.31. Therefore, the `377 patent in view of Weigun et al. would have rendered claims 9-11 obvious.
In terms of claims 12-14, the further cited step of “detaching the mammalian cells from the siliceous surface of the buoyant hollow particles”, “collecting the detached mammalian cells by sedimentation or centrifugation”, and “adding additional cell culture media or additional buoyant hollow particles” are routine cell culture procedures and at grasp of one skilled in the art. These experimental protocols are disclosed in Fundamental Techniques in Cell Culture Lab Handbook, 4th Ed., (2018), Millipore Sigma. (e.g. 14.4 Protocol 3- Subculture of Adherent Cell Lines” at page 39-40). In addition, Falipou et al. teaches a simple method of fix biological species (e.g., mammalian cells of CD45 rat cells) to silica-based surface including glass slides and silica beads, which are hollow, low-density silica microbeads (see Abstract at p.81).
In terms of claim 15 where in the average seeding density is 3-50 adherent cells/buoyant hollow particle, is a routine experimental optimization further in view of the disclosure by Fundamental Techniques in Cell Culture Lab Handbook, 4th Ed., (2018), Millipore Sigma. (e.g. 14.4 Protocol 3- Subculture of Adherent Cell Lines” at page 39-40). Optimization of the range of each active agents in the combined composition is a routine practice, not inventive practice. It has been well established that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955). 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)). "Only if the results of optimizing a variable are unexpectedly good can a patent be obtained for the claimed critical range." In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (quotations omitted).
In terms of claim 16 wherein said buoyant hollow particles with the mammalian cells attached separate from said media in less than about 2 minutes, it would have been obvious to one skilled in the art because Rapid Separation Techniques (< 2 Minutes) such as Gravity Sedimentation (Settling), Filtration (Cell Strainers), Acoustic Separation (Enzyme-Free), and using Microcarrier Separation Bags are the most common techniques for separating mammalian cells attached carriers from their cell culture medium.
Conclusions
Claims 9-16 are rejected.
Claims 1-8 remain withdrawn.
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's submission of an information disclosure statement under 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p) on 10/17/2022 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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 mailing date of this final action.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong L. Chu, whose telephone number is (571)272-5759. The examiner can normally be reached on M-F 8:30am-5:00pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amber R. Orlando can be reached on 571-270-3149. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/YONG L CHU/Primary Examiner, Art Unit 1731
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