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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submissions on 12/16/2025 has been entered. New claim 16 is added. Claims 1-16 are pending. Claims 1-8 remain withdrawn. Claims 9-16 are under examination on the merits.
Response to Arguments/Amendments
Claim rejection under 35 U.S.C.§102(a)(1)
Applicant’s argument over the rejection of claims 9-15 is on the ground that the '377 patent does not disclose a method for culturing cells, said method comprising particles that are less dense than a media, as disclosed in independent claim 9. Instead, '377 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. The microcarriers disclosed in '377 are not less dense than the media, but are in fact the same density as the media, which is in contrast to the claimed invention. Applicant’s argument is not persuasive. As being acknowledged by Applicant that 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 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) 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, and present claim 9 is also drawn to a method for culturing cells using buoyant hollow particles.
In terms of Applicant’s argument that “The present application discloses that the use of floating buoyant hollow particles enables easy separation of cells from the carriers because after the cells are detached from the carrier, there is easy separation of the cells from the microcarriers because the cells sink while the carrier floats. See e.g., the present application, para. [0029]. This advantageous separation method would not be possible with the microcarriers disclosed in '377 because rather than floating to the top of the media, the microcarriers are stuck in suspension in the media, due to the substantially equal densities”, easy separation of the cells from the microcarriers is irrelevant to with the claimed method nor the '377 patent. The `377 patent indeed anticipates claims 9-14. The rejection is maintained.
Claim rejection under 35 U.S.C.§103(a)
Applicant’s argument over the rejection of claims 12-15 is maintained because 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 must be 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) 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, and present claim 9 is also drawn to a method for culturing cells using buoyant hollow particles. Therefore, the '377 publication in view of Cell Culture and Falipou et al. would have rendered claims 12-15 obvious. The rejection is maintained.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 9-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by GB2112377B (“the `377 patent”) to Downs et al., published 07/20/1983.
Applicant’s claim 9 is drawn to a method for culturing cells, the method comprising providing a plurality of buoyant hollow particles, the buoyant hollow particles comprising a siliceous surface, wherein the buoyant hollow particles are less dense than a media; contacting the buoyant hollow particles with a media comprising a plurality of mammalian cells; allowing the mammalian cells to attach to the siliceous surface of the buoyant hollow particles; and culturing the mammalian cells on the siliceous surface of the buoyant hollow particles by agitation, to yield the cell culture.
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”. Therefore, the `377 patent anticipates claim 9.
In terms of claim 10 further comprising separating the buoyant hollow particles with the mammalian cells attached from the media, see p.8, lns. 17-26.
In terms of claim 11 wherein the separating step comprises allowing the buoyant hollow particles with the mammalian cells attached to float to an upper surface of the media, the `377 patent (claim 4) discloses the microcarriers have an average density substantially equal to said predetermined density such that said microcarrier is buoyantly suspended in said medium, which means floating to an upper surface of the media.
In terms of claims 12-14, they are the must steps for cell culturing of anchorage-dependent cells. See “Cell Culture” and “Tissue Culture” Wikipedia, and their cited references thereof.
Alternatively, claims 9-16 are rejected under 35 U.S.C. 103(a) as following:
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”), and Falipou et al., Sensors and Actuators, (1999), v.74, p.81-85.
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 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 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) 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, and present claim 9 is also drawn to a method for culturing cells using buoyant hollow particles.
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.
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.
/YONG L CHU/Primary Examiner, Art Unit 1731