DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 29 April 2026 has been entered.
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.
The factual inquiries 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 1, 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Luo (CN 206308363) in view of Ali (US 20200140799), Chotteau (US 20140011270) and Kreuzmann (US 20110207165).
With respect to claim 1, Luo discloses a bioreactor system for culturing cells without cell walls that includes a container comprising a hollow cylinder with a diameter of D1 and a height of H1, and a hollow circular truncated cone with an upper diameter of D2, a lower diameter of D3 and a height of H2, wherein the hollow cylinder is connected to a top surface of the hollow circular truncated cone, and D1=D2.
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An oscillator (Figure 1:102) is configured to make the container move in an eccentric motion according to a certain eccentricity and rotational speed (“the oscillator is provided with a motor, a main transmission eccentric shaft and the supporting eccentric shaft, a main transmission eccentric shaft and the supporting eccentric shaft joint between the support and a wobble plate via a bearing, a motor drives the main transmission eccentric shaft and thus drive rocker winding vertical axis producing a horizontal oscillating motion”). Figures 1, 2 and 8 appear to show a ventilation device that introduces oxygen-containing gas from an upper position of the container to the inside of the container, such that a culture solution filled in the container is exposed to an oxygen-containing gas. There does not, however, appear to be an accompanying description in the text that describes this function.
Ali discloses a bioreactor system for culturing cells without cell walls comprising a container (Figure 5:502) and an oscillator (Figure 5:510). A ventilation device (Figure 5:505) is configured to introduce an oxygen-containing gas from an upper portion of the container to the inside of the container (“A fourth port 505 is fluidically connected to an external oxygen source via a fifth fluid conduit 511”). This is taught in paragraphs [0031]-[0033].
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Luo ventilation device introduces oxygen-containing gas from an upper position of the container to the inside of the container, such that a culture solution filled in the container is exposed to an oxygen-containing gas, in the event that Luo does not already do this. Both Luo and Ali are concerned with monitoring dissolved oxygen concentration in the fluid during cell culture, and Ali shows the provision of an external oxygen source is an effective way to replenish oxygen in a headspace gas when low concentration levels are detected. Ali clearly shows that oxygen delivery is best accomplished by allowing oscillated fluid to mix with oxygenated gas introduced from above the top surface of the fluid.
As for the limitation “wherein the bioreactor system is characterized by a ratio…a turbulence kinetic energy…and a flow field shear rate…”, it is noted that the Luo oscillator and ventilation device are configured to produce fluid having the required state of motion, turbulence and flow field shear rate merely by changing their operational settings. Apparatus claims cover what a device is, not what a device does. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP 2114.
Luo and Ali still differ from the Applicant’s invention because they do not appear to teach the claimed reactor dimensions and operation.
Chotteau discloses a bioreactor system for culturing cells without cell walls comprising a container (Figure 4:4) and an oscillator (Figure 4:9). Chotteau teaches in paragraph [0057] that it is common to operate such a bioreactor at a wide range of sizes (e.g., 200 mL to 500 L) and oscillation speeds. For example, Chotteau teaches rocking at 24-55 rpm.
Kreuzmann discloses a system for culturing cells in a flask agitated using an oscillator. The Tables in Examples 3 and 4 show that the eccentricity of the oscillator is 50 mm. Paragraphs [0019]-[0027] and [0096]-[0106] teach that rotational movement of the oscillator may be approximately 60 rpm and may vary based on certain observable interrelated parameters, such as cell density, gas concentration and pH.
Before the effective filing date of the claimed invention, it would have been obvious to construct and operate the Luo bioreactor system according to the claimed dimensions and ranges. As evidenced by Chotteau and Kreuzmann, changing bioreactor size, shape and oscillation rate affects nutrient and gas transfer across the culture fluid, as well as cell growth and product generation. Furthermore, it is noted that mere changes in size and shape that do not substantially affect device functionality, or do so in a predictable manner, are considered to be prima facie obvious. See MPEP 2144.04. It is well within the ability of one of ordinary skill to scale-up or scale-down reactor dimensions according to known principles. Indeed, the Chotteau reference indicates that it is well within the ability of one of ordinary skill to scale up or scale down a bioreactor across a wide range of sizes (e.g., 5 mL to 3,000 L). The Luo reference teaches a reactor having essentially the same shape as the claimed container, and there is no reason to believe that the Luo reactor could not be configured to have D1, D2, D3, H1 and H2 values that fall within the broad claim ranges.
With respect to claim 3, Luo, Ali, Chotteau and Kreuzmann disclose the combination as described above. Luo and Ali both teach disposable culture bags used for holding a culture solution. Luo specifically states that the culture bag assumes the shape of the container when placed into it and expanded (“the flexible bag when deployed with the culture container cavity of corresponding shape”).
With respect to claim 4, Luo, Ali, Chotteau and Kreuzmann disclose the combination as described above. Luo further shows that the disposable culture bag includes a multifunctional cover plate with a plurality of connecting holes.
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Response to Arguments
Applicant's arguments filed 29 April 2026 and 15 May 2026 have been fully considered but they are not persuasive.
The claims establish that certain S/V, kinetic energy and shear rate conditions are obtainable when predetermined combinations of bioreactor geometry and operation are present. The Luo reactor has the same shape and design as the claimed container, so if D1, D2, D3, H1, H2 are set to any of the values in the claimed groups, then it stands to reason that the same S/V, kinetic energy and shear rate conditions would be realized. Again, apparatus claims cover what a device is, not what a device does. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP 2114. Here, the resultant S/V, kinetic energy and shear rate values discussed in the claims are a product of the physical characteristics of the bioreactor container and its mode of operation, which are all recognized and documented in the cited prior art.
The Luo reactor is structurally identical to the reactor described in Applicant’s specification.
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There is nothing of record to suggest that they would be characterized by different culture conditions when subjected to the same operating conditions. No structural feature (baffles? impeller? flow-directing plates? growth substrates?) is alleged to be missing from Luo to explain and account for the purported difference in operation. Because the prior art reactor is structurally equivalent to the claimed reactor, the burden now shifts to applicant to establish that the prior art does not possess the characteristic relied on. See MPEP 2114.
Ali, Chotteau and Kreuzmann are provided as further evidence that the broad ranges of D1, D2 as 400-2,997 mm, D3 as 80-190 mm, H1 as 149-867 mm, H2 as 98-684 mm, V as 5-3,000, rotational speed as 24-55 rpm and eccentricity as 30-65 mm are all well known in the art and characterized by a routine and predictable operation. The narrower range recitations set forth in the claim are optional (“or”) and not required. As noted in the rejection above, mere changes in size and shape that do not substantially affect device functionality, or do so in a predictable manner, are considered to be prima facie obvious. See MPEP 2144.04. It is well within the ability of one of ordinary skill to scale-up or scale-down reactor dimensions according to known principles. Indeed, the Chotteau reference indicates that it is well within the ability of one of ordinary skill to scale up or scale down a bioreactor across a wide range of sizes. The Luo reference teaches a reactor having essentially the same shape as the claimed container, and there is no reason to believe that the Luo reactor could not be configured to have D1, D2, D3, H1 and H2 values that fall within the broad claim ranges
Conclusion
This is a non-final rejection.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799
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