DETAILED ACTION
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, 5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Rakoczy (EP 3088509) in view of Chang (US 7662615) and/or Felder (US 20050054101).
With respect to claim 1, Rakoczy discloses an apparatus comprising a stationary member (Figure 6:3), a magnetic field generator (Figure 1:7), and a rotating member (Figure 6:19). The rotating member is configured to rotate within the stationary member, and the magnetic generator is configured to generate a magnetic field on magnetic particles disposed within a cell culture medium. This is described in paragraphs [0041]-[0044]. Rakoczy, however, does not appear to teach that the magnetic generator is controlled by a controller configured to generate a variable magnetic field on the magnetic beads.
Chang discloses a system for cultivating cells in a culture medium supported by a stationary member. A magnetic field generator configured as an electromagnetic coil (Figure 1A:16) surrounds the stationary member and produces a magnetic field that is applied on the cells. Column 2, line 52 to column 3, line 35 teach that a controller (Figure 1A:18) is configured to control the magnetic field generator to generate a variable magnetic field (“Additionally, the electromagnetic stimulator 18 is able to adjust the waveform, frequency, and amplitude of the first signals 17, so as to change the pulse pattern, frequency, and intensity of the induced electromagnetic field”).
Felder discloses an automated cell culture system comprising a stationary member configured to retain a cell culture medium comprising magnetic beads (“microcarriers”). A magnetic field generator configured as electromagnetic coils or magnets (see Figs. 6-10) is used to move the magnetic beads in the culture medium. A controller (Figure 4:“Control System”) is configured to generate a variable magnetic field on the magnetic beads. This is described in paragraphs [0030]-[0032] and [0054]-[0058] (“By computer-controlled activation of the magnets and alteration of their polarity, many different microcarrier paths can be effected for stirring, media changing, cell adhesion operations, or cell harvesting”).
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Rakoczy system includes a controller configured to regulate the generation of a variable magnetic field on magnetic beads in the culture medium. Chang and Felder each teach that different cell types respond differently to variable stimulation during culture, and that it is important to adjust the applied electromagnetic field to respond to detected cell growth and activity. Those of ordinary skill would have further understood that a variable pulsed electromagnetic field would enhance mixing of the magnetic beads suspended in the culture medium and enable additional operations, such as product separation and cell harvesting.
As for limitations requiring the rotating member to apply a rotational force to the magnetic beads in a first direction and the magnetic field generator to apply a magnetic force to the magnetic beads in a second direction that is different than the first direction, it is noted that Rakoczy, Chang and Felder each teach the generation of magnetic fields that may be applied in different directions with different forces and as pulses. For example, Felder expressly shows magnetic force applied in all four cardinal directions in at least Fig. 2. Fig. 8 shows magnetic force applied at offset and varying angles. Paragraph [0065] expressly states that the direction of the applied magnetic field may be changed to produce different effects on the cells and magnetic particles (“changes in cellular physiology or biochemistry are measurable in response to an externally applied magnetic field that allows for changes in microcarrier internal or external kinetic energy, for example, in one embodiment, rotation according to a user programmable profile of speed, direction, amplitude, and temporal profile (such as pulsatile, ramping, square wave, and other user definable profiles)”, emphasis added). Furthermore, it is well established that 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.
With respect to claim 3, Rakoczy, Chang and Felder disclose the combination as described above. Rakoczy further shows that the cell culture medium is located between the stationary member and the rotating member.
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Claims 8 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Rakoczy (EP 3088509) in view of Chang (US 7662615) and/or Felder (US 20050054101) as applied to claim 1, and further in view of Traelnes (US 3604690) and Shkidchenko (US 4379846).
With respect to claims 8 and 10, Rakoczy, Chang and Felder disclose the combination as described above, however do not appear to teach that the rotating member comprises discs that are interdigitated with a plurality of annular surfaces extending from the stationary member.
Traelnes discloses an agitation system for cell culture comprising a stationary member having a plurality of baffle surfaces (Figure 1:4). The baffle surfaces are interdigitated with a plurality of rotating discs (Figure 1:3).
Shkidchenko discloses a cell culture system comprising a stationary member having a plurality of annular surfaces (Figure 1:8). The annular surfaces are interdigitated with a plurality of rotating discs (Figure 1:7).
Before the effective filing date of the claimed invention, it would have been obvious to modify Rakoczy to include essentially any rotating member configuration suitable for agitating a cell culture solution. Traelnes and Shkidchenko show how rotating discs that interact with annular baffles surfaces may improve mixing and aeration (“at a high-power input and high aeration rate a much greater rate of oxygen absorption is obtained”) while providing a uniform distribution of cells and nutrients.
With respect to claims 11 and 12, Rakoczy, Chang, Felder, Traelnes and Shkidchenko disclose the combination as described above. Traelnes further shows that the plurality of discs 3 include a plurality of apertures (Figure 2:11) through which cells and magnetic beads may travel. Shkidchenko additionally states that the discs are fabricated from a capillary porous material and therefore include a plurality of apertures.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Rakoczy (EP 3088509) in view of Chang (US 7662615) and/or Felder (US 20050054101) as applied to claim 1, and further in view of Jones (US 20120045834).
Rakoczy, Chang and Felder disclose the combination as described above, however do not appear to teach that the rotating member comprises a plurality of randomly oriented fibers.
Jones discloses a rotating member (Figure 1:10) for mixing cell culture fluid within a bioreactor defined by a stationary member. See Fig. 8. Paragraphs [0057] and [0058] state that the rotating member may be made from a variety of different materials, including carbon fiber and fiberglass.
Before the effective filing date of the claimed invention, it would have been obvious to fabricate the Rakoczy rotating member from essentially any material recognized in the art as being biocompatible and suitable for use as a mixing element. Jones teaches that carbon fiber and fiberglass impellers (which include randomly oriented fibers) are an inexpensive and durable option and may be manufactured by standard techniques.
Response to Arguments
Applicant's arguments filed 14 April 2026 have been fully considered but they are not persuasive.
Applicant argues that Rakoczy does not teach a controller configured to generate variable magnetic fields, and that the Chang and Felder references do not provide a reason or motivation to do so. However, Felder expressly states in in paragraphs [0030]-[0032] and [0054]-[0058] that automated regulation of an applied magnetic field may be used to advantageously effect cell growth and development (“By computer-controlled activation of the magnets and alteration of their polarity, many different microcarrier paths can be effected for stirring, media changing, cell adhesion operations, or cell harvesting”). Similarly, Chang discusses in at least column 2, line 52 to column 3, line 35 teach that a controller is configured to control the magnetic field generator to generate a variable magnetic field (“Additionally, the electromagnetic stimulator 18 is able to adjust the waveform, frequency, and amplitude of the first signals 17, so as to change the pulse pattern, frequency, and intensity of the induced electromagnetic field”). It is prima facie obvious to apply a known technique (here, a computer-controlled variable electromagnetic field) to a known device ready for improvement to yield predictable results. See MPEP 2143.
Applicant argues that Chang and Felder teach away from the claimed invention because they do not disclose agitation of suspended microcarriers. In response, it is noted that Rakoczy is the primary reference and already teaches these features. Chang and Felder are instead relied upon for disclosing the state of the art regarding automation, computer control and the generation of a variable magnetic field. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant lastly argues that the cited prior art references do not teach applying a rotational force in a direction that is different than the direction of an applied magnetic force. At a minimum, however, Felder shows in Figs. 2-4 that magnetic forces may be applied to the cells and microcarriers at essentially any and every direction.
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Fig. 8 of Felder shows magnetic force applied at offset and varying angles. Paragraph [0065] expressly states that the direction of the applied magnetic field may be changed to produce different effects on the cells and magnetic particles (“changes in cellular physiology or biochemistry are measurable in response to an externally applied magnetic field that allows for changes in microcarrier internal or external kinetic energy, for example, in one embodiment, rotation according to a user programmable profile of speed, direction, amplitude, and temporal profile (such as pulsatile, ramping, square wave, and other user definable profiles)”, emphasis added).
Conclusion
THIS ACTION IS MADE FINAL. 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 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
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