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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05 November 2025 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, 5-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Ogata (JP H03272678) in view of Konishi (US 20160355774), and further in view of Shor (US 20160108356) and/or Van Wezel (US 488294) and/or Mueller (US 4276384).
With respect to claims 1, 5 and 10, Ogata discloses a perfusion apparatus comprising a bioreactor having a rotatable shaft (Figure 1:41) connected to an impeller (Figure 1:42) and a motor (Figure 1:44). Ogata teaches that the bioreactor may have a diameter of approximately 220 mm. Figure 1 depicts the bioreactor as having a height approximately equal to the diameter and a cylindrical shape, and therefore it is understood that the bioreactor may have a volume of about 4 L. Regardless, it is prima facie obvious to adjust bioreactor volume to arrive at a desired value, especially within the broad range of 3 L to 2,000 L. A hollow tubular member for perfusing the fluid from the bioreactor is provided, wherein the hollow tubular member has a first end defining a first opening and a second and opposite end defining a second opening. A filter member (Figure 1:5A) is located and directly attached to the second end of the hollow tubular member, such that the filter member completely surrounds and encloses the second opening. Ogata, however, does not expressly teach the claimed dimensions relating to the configuration of the hollow tubular member and filter member.
Konishi discloses a perfusion apparatus comprising a bioreactor having a hollow tubular member (Figure 4:17) for perfusion fluid from the bioreactor. Paragraph [0098] states that the hollow tubular member has a diameter from about 2 mm to about 40 mm and a second open end (Figure 4:17b), wherein the second end 17b is defined by a straight section. At least Figures 1 and 4 show that the straight section at the second end has a length greater than the length of the bioreactor. A first open end of the hollow tubular member interfaces with a pump (Figure 1:10). A filter member (Figure 4:21) is directly attached to the straight section at the second end and completely surrounds and encloses the second opening. This is shown in at least Figs. 1-6. From the Figures, it is apparent that the surface area of the filter member is significantly greater than the cross-sectional area of the second opening, such that the ratio between the cross-sectional area of the second opening and the surface area of the filter member is between about 1:20 to about 1:200. More specifically, Konishi discusses dimensions for the second opening (diameter of 1.8 mm) and the filter member (diameter of 8 mm; length of 15 mm) that would put the ratio at about 1:150. Paragraphs [0093] and [0104] teach that the hollow tubular member is configured to withdraw fluid medium from the bioreactor at a flow rate of at least 50% of the bioreactor volume per day.
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Ogata bioreactor includes a hollow tubular member having a diameter from 2-40 mm and a filter member that has a surface area at least 20 times greater than the cross-sectional area of the second opening of the tubular member. Konishi teaches that these dimensions are common in the bioreactor art where a filter member is used to treat withdrawn perfusion fluid. Mere changes in size or shape that do not substantially affect device operation, or do so in a predictable, art-recognized manner, are considered to be prima facie obvious. See MPEP 2144.04. Konishi further teaches that hollow tubular members and filter members of these sizes and shapes are suitable for withdrawing at least 50% of the bioreactor volume per day, which provides effective transfer of nutrients and oxygen to growing cells and removal of waste products.
With respect to the limitation “wherein the hollow tubular member defining at least one straight section includes a first straight section, a second straight section, and an angled straight section…”, Ogata shows that the hollow tubular member includes a first straight section, a second straight section, and an angled section between the first and second straight section. The angled section is approximately 90° and functions to direct the hollow tubular member and filter member downward so that they do not contact the rotating shaft and impeller at the center of the bioreactor.
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Although Ogata shows that the 2nd vertical axis is parallel to the vertical axis of the bioreactor, Ogata does not show that the 1st straight section is also parallel to a vertical axis of the bioreactor.
Shor discloses a perfusion apparatus comprising a bioreactor comprising a filter member (Figure 6:604) configured to treat fluid as it is removed from the bioreactor via a hollow tubular member (Figure 6:611). Shor shows a variety of additional hollow tubular members that are “bent” (as described in paragraph [0083]) to avoid contact with the impeller 602.
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Van Wezel discloses a perfusion apparatus comprising a bioreactor having a volume of approximately 3 L (see Tables I and II). A filter member (Figure 6:62,64) is used to treat fluid as it is removed from the bioreactor via a hollow tubular member (Figure 6:5). The hollow tubular member 5 is shown to include a first straight section, an angled section, and a second straight section, wherein the first and second straight sections are parallel to a vertical axis of the bioreactor.
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Mueller discloses a perfusion apparatus comprising a bioreactor comprising a plurality of hollow tubular member (Figure 1:7,8,9) configured to deliver and remove gases and compounds from the interior of the reactor. The hollow tubular members are shown to include a first straight section, an angled section, and a second straight section, wherein the first and second straight sections are parallel to a vertical axis of the bioreactor.
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Before the effective filing date of the claimed invention, it would have been obvious to orient the Ogata hollow tubular member such that it includes a first straight section and a second straight section that are both parallel to a vertical axis of the bioreactor. As evidenced by Shor, Van Wezel and Mueller, it is well within the ability of one of ordinary skill to connect and position hollow tubular members in a bioreactor to produce a variety of different fluid flow configurations. More specifically, these references show how hollow tubular members may be vertically oriented and include angled sections to avoid contact with other bioreactor elements. Mere changes in design (such as the provision of 1st, 2nd, 3rd, etc. vertical straight sections) that produce a predictable and known effect on device operation are considered to be prima facie obvious. See MPEP 2144.04.
With respect to claim 6, the cited references disclose the combination as described above. Konishi further teaches in paragraph [0052] the hollow tubular member is made at least in part from stainless steel
With respect to claim 7, the cited references disclose the combination as described above. The Ogata device may be configured as a single-use reactor.
Claims 2-4 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Ogata (JP H03272678) in view of Konishi (US 20160355774) and further in view of Shor (US 20160108356) and/or Van Wezel (US 488294) and/or Mueller (US 4276384) as applied to claim 1, and further in view of Larsen (9376655).
With respect to claims 2-4, the cited references disclose the combination as described above, however do not teach a filter member pore size between 60-150 microns.
Larsen discloses a perfusion apparatus comprising a hollow tubular member (Figure 3:151) having a first upper end defining a first opening and a second lower end that is opposite the first end and defines a second opening. A filter member (Figure 3:170) is attached to the second end of the hollow tubular member and completely surrounds and encloses the second opening. This is described in at least column 6, line 8 to column 8, line 12. Larsen further teaches in at least column 7, lines 9-31 that the filter member comprises a porous mesh that is characterized by a pore size as great as 100 microns.
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Ogata filter member has a porous mesh with an average pore size between 60-150 microns. Larsen teaches that pores of this size are effective for allowing individual cells to pass through while retaining larger beads, spheres and other cell carriers. Larsen states that this is important because it allows the cell carriers to be isolated, collected and re-used.
With respect to claim 8, the cited references disclose the combination as described above. Konishi and Larsen additionally teach hollow tubular members made from plastics. Thermoplastic polymers (e.g., acrylic, polyester, polypropylene, polystyrene, nylon and Teflon) are well known in the art, and it would have been obvious to use any of them when making the Ogata hollow tubular member. Larsen additionally teaches in at least column 7, lines 9-31 that the filter member includes a polyamide mesh.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over either Ogata (JP H03272678) in view of Konishi (US 20160355774) and further in view of Shor (US 20160108356) and/or Van Wezel (US 488294) and/or Mueller (US 4276384) as applied to claim 1, and further in view of Ho (US 20130071872).
The cited references disclose the combination as described above, however do not expressly state that the hollow fiber member and the filter member are movably enclosed in a collapsible bellows.
Ho discloses a bioreactor (Figure 24:401) in communication with a means (Figure 24:407) for withdrawing material from the interior of the reactor. The means for withdrawing material is movably enclosed in a collapsible bellows (Figure 24:045), wherein the collapsible bellows includes a sterile connection port (Figure 23:404’) that is mated with a sterile connection port (Figure 23:404) of the bioreactor. This is described in paragraphs [0052] and [0053].
Before the effective filing date of the claimed invention, it would have been obvious modify the Ogata perfusion apparatus by enclosing the hollow tubular member and filter member in a collapsible bellows. Ho teaches that this allows a sampling means to be aseptically connected to a bioreactor in a manner in which communication with the interior of the bioreactor is maintained only during sampling. Those of ordinary skill would have recognized that this would be beneficial because it would allow the Ogata hollow tubular member and filter member to be retracted out of the bioreactor when they are not being used, and thereby ensure that the hollow tubular member and filter member would not interfere with other mechanical devices and the culture solution during fermentation.
Response to Arguments
In response to the amendment filed 05 November 2025, the previous rejections have been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the Shor, Van Wezel and Mueller references which show how it is known in the art to provide a perfusion apparatus with first and second straight sections separated by an angled section, such that the first and second straight sections are parallel to a vertical axis of the reactor.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at (571) 272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NATHAN A BOWERS/ Primary Examiner, Art Unit 1799