DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-9, 11-12, and 14-40, of record 7/28/2026, are pending. Claims 22-29 are amended. Claims 10 and 13 are cancelled. Claims 1-9, 11-12, 14-21, and 30-40 remain withdrawn.
Status of Prior Rejections/Response to Arguments
RE: Objection to the specification:
The amendment to the specification is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claims 22-29 under 35 U.S.C. 112(b):
The amendment of claim 22 is effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claims 22-29 under 35 U.S.C. 103 over Nahmias et al. (US 20210395690 A1) in view of Whitford et al. (BioProcess International, 2009), Gramer (US 6001585 A), Kallury et al. (US 20040171169 A1), Yamamoto et al. (Journal of Chemical Engineering of Japan, 2012), and Miller (US 20110091604 A1):
The applicant asserts that:
No single reference or combination of the cited references teach or suggest all of the claimed limitations (Applicant Remarks, page 13-14).
Most of the references use non-edible, synthetic hollow fibers and fail to provide guidance on properties that would be appropriate in the context of meat production, therefore one would have no reasonable expectation of success (Applicant Remarks, page 14-15).
Whitford et al. do not disclose the same design philosophy as the instant invention with respect to void space (Applicant Remarks, page 15-16).
Gramer teaches a bioreactor for cell line screening rather than structured meat production (Applicant Remarks, page 15-16).
Yamamoto et al. teach a research bioreactor comprising a gel matrix and magnetically accumulated cells in its void space rather than biomass for food, and its seeding method is not applicable to the claimed invention (Applicant Remarks, page 15-16).
Kallury et al. teach methods for analytical chemistry sample preparation, which serves as non-analogous art (Applicant Remarks, page 15-16).
Miller teaches only 2D culture of synthetic meat on polymer substrates, and application of the teachings of Miller to confluency constitutes impermissible hindsight reconstruction (Applicant Remarks, page 15-16).
The prior art does not teach or suggest the claimed parameters for fiber density and void space (Applicant Remarks, page 16).
The applicant’s arguments are not found wholly persuasive. Per MPEP 2141(III), the prior art is not required to teach or suggest all claim limitations when a person of ordinary skill in the art—here, one who is capable of designing and implementing protocols for the production of synthetic meats in bioreactors or the like—would have found them to be obvious. Because the ordinary artisan would understand that hollow fiber membranes have numerous applications, the teachings of Kallury et al. on the general porosity of commercial hollow fiber cartridges would still be reasonably pertinent and constitute analogous art, even if the reference was itself directed to a different problem. See MPEP 2141.01(a)(I). Further, conditions that enable the culture of cells on non-edible hollow fibers could readily be applied to edible fibers, as references are prior art for all that they contain or would have reasonably suggested to one of ordinary skill in the art. See MPEP 2123(I). It is also noted that the teachings of Whitford et al., Gramer, and Yamamoto et al. are relied upon in the rejection of record only for general setup of hollow fiber cell culture perfusion bioreactors, hollow fiber dimensions appropriate for culturing cells in bioreactors, and an exemplary seeding density for forming muscle tissue constructs in a hollow fiber bioreactor, respectively, all of which is directly relevant to the teaching of Nahmias et al. that cultured meat can be produced using edible hollow fiber cartridges.
Regarding the assertion of impermissible hindsight reconstruction, it must be recognized that any judgment on obviousness is, in a sense, necessarily a reconstruction based upon hindsight reasoning. But, so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Miller indicates that culturing of synthetic meat products is completed when a uniform and mechanically integral piece has formed (See ¶0016). While Miller is specifically concerned with sheets of meat, the need for uniformity and mechanical integrity can be readily recognized and applied to other forms of synthetic meat by one of ordinary skill. Uniformity and mechanical integrity would also necessarily require a very high degree of cell coverage and therefore encompass a very high degree of confluency.
However, the amendment to claim 22 require a void space of 25-75% of the total cartridge volume and a hollow fiber density of about 40-120 cm2, limitations which were not previously considered, is effective to obviate the rejection. The rejection is withdrawn in favor of a new rejection.
New Rejections
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 22-29 are rejected under 35 U.S.C. 103 as being unpatentable over Nahmias et al. (US 20210395690 A1), of record, evidenced by FiberCell (Product brochure, 2026), in view of Whitford et al. (BioProcess International, 2009), of record, Gramer (US 6001585 A), of record, Kallury et al. (US 20040171169 A1), of record, Yamamoto et al. (Journal of Chemical Engineering of Japan, 2012), of record, and Miller (US 20110091604 A1), of record.
Regarding claims 22-23 and 25-28: Nahmias et al. teach methods of culturing adherent connective tissue cells (See ¶0005). The methods can be used to produce a cultured meat (See v0025 and ¶0060-0061). The cells can be fibroblasts, adipocytes, myofibroblasts, and myocytes (See ¶0046). The cells can be cultured on a matrix, that can comprise collagen, soy or pea protein, or hydroxypropyl cellulose (which reads on “hydrocolloid”), and the matrix can be an edible hollow fiber cartridge with fibers can be made from edible natural or synthetic polymers (See ¶0063-0066). The cells form a mass surrounding the hollow fibers (which reads on “seeding the void space between the hollow fibers”) (See ¶0066).
Nahmias et al. do not expressly teach the amount of void space in the cartridge, however, the FiberCell C3008 cartridge is taught as an example of an edible hollow fiber cartridge (See ¶0066). FiberCell teaches that the C3008 cartridge has a packing density of 38% (which reads on “the void space being 25 to 75% of the total volume of the hollow fiber cartridge”) (See page 8).
Nahmias et al. also do not expressly teach the cartridge and reactor setup, the dimensions of the hollow fibers, the seeded cell density, or the final cell confluency.
Whitford et al. teach that hollow fiber perfusion bioreactors comprise semipermeable hollow fibers set in parallel array within a tubular housing or cartridge and attached to each end of the cartridge so that any liquid entering the cartridge will flow through the interior of the fibers (which reads on “each of said hollow fibers has a first end and a second end wherein said first end and said second end are positionally opposed to each other and wherein said hollow fibers are arranged in parallel to each other” and “the first ends of said hollow fibers are secured in a first holding device and the second ends of said hollow fibers are secured in a second holding device, the first and second holding devices being orientated parallel to each other, wherein at least one holding device allows for flow of fluids to an interior space of the hollow fibers” (See page 54, col. 2, full ¶2 and col. 3, v1 and fig. 1-2 and 5). The cartridge housing comprises inlet and outlet ports for connecting medium and waste reservoirs using a pump system (See fig. 2 and 5). The medium supplied through the hollow fiber lumens perfuses into the extracapillary space holding the cells (See fig. 1).
Gramer teaches hollow fiber bioreactors and components for growing cells (See Abstract). Commercially available hollow fibers are suitable for use in the bioreactor (See col. 7, line 57-60). Preferred hollow fibers have a wall thickness of between about 2-200 microns (which reads on “a wall thickness of about 0.05 mm to about 0.4 mm”) and an inner diameter of between about 20-1000 microns (which, in view of the preferred wall thickness, reads on “an outer diameter of about 0.2 mm to about 2.0 mm”) (See col. 8, line 18-27).
Kallury et al. teach that typical commercially-available hollow fibers have a porosity of about 30-80% (See ¶0047).
Yamamoto et al. teach the seeding of skeletal muscle cells in a hollow fiber bioreactor at 8.7 × 107 cells/ml (which reads on “a density of about 105 cells/ml to about 108 cells/ml”) for forming muscle tissue constructs (See page 6, full ¶1).
Miller teaches methods for producing synthetic meat (See Abstract). Miller teaches that, generally, completion of the growth process may be considered when a sheet of meat has been formed and that the substrate on which the cells are grown may exit the bioreactor (which reads on “removing said hollow fiber cartridge from the hollow fiber cell culture reactor”) after cell growth has formed a uniform and mechanically integral film of meat (which reads on “cells are cultured until achieving about… 99% confluency”) (See ¶0016).
It would have been obvious to one having ordinary skill in the at prior to the effective filing date of the claimed invention to modify the method of Nahmias et al. to comprise the hollow fiber cartridge and bioreactor setup taught by Whitford et al. One would be motivated to make this modification because Whitford et al. teach these setups as typical for culturing cells in hollow fiber cartridges (See fig. 2 and 5). There would be a reasonable expectation of success in doing so because Nahmias et al. teach that culturing cells to form a meat product can be performed using an edible hollow fiber cartridge (See ¶0066).
It would have also been obvious to modify the method of Nahmias et al. to comprise the dimensions and porosity ranges taught by Gramer and Kallury et al. for the hollow fibers. One would be motivated to make this modification because Gramer teaches these physical properties as suitable for hollow fibers in bioreactors wherein membranes separate cells and medium channels (See col. 7, line 57-60 and col. 8, line 18-27). There would be a reasonable expectation of success in making this modification because the edible hollow fiber cartridges of Nahmias could be readily modified to have these properties. Additionally, a packing density of 38%, exemplified in the FiberCell cartridge disclosed by Nahmias et al., would encompass 40-120 fibers/cm2 at the fiber dimensions taught by Gramer; for example, hollow fibers having an outer diameter of approximately 650 or 1100 microns that are packed at a density of 38% yield 120 or 40 fibers/cm2, respectively, using the equation that fibers/cm2 = (packing density)/(cross-sectional area of one fiber in cm2).
It would have been further obvious to modify the method of Nahmias et al. to comprise the seeding density of 8.7 × 107 cells/ml taught by Yamamoto et al. One would be motivated to make this modification because the use of such a density by Yamamoto et al. suggests that it is appropriate for generating skeletal muscle constructs in a hollow fiber bioreactor, and such a modification could be readily made.
Finally, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Nahmias et al. to comprise culturing the cells to approximately 99% confluency to form a uniform and mechanically integral sample. One would be motivated to make this modification because Miller suggests that ending the culturing process when the cells have formed a uniform sheet of meat is appropriate (See ¶0016). Such a modification could be readily made.
Regarding claim 24: Following the discussion of claims 22-23 and 25-28, Nahmias et al. do not expressly teach removing the hollow fibers from being held by the cartridge. However, because Nahmias et al. expressly teach that the fibers of the cartridge are edible (See ¶0066) without teaching that other parts of the cartridge are edible, one of ordinary skill in the art would find it obvious to remove the myocyte-laden hollow fibers from their holders upon harvesting.
Regarding claim 29: Following the discussion of claims 22-23 and 25-28, Nahmias et al. teach that coloring agents, flavoring agents, and preservatives may be present (See ¶0081) but do not expressly teach infusion of the hollow fiber interior or void space. However, it would have been obvious to one of ordinary skill in the art that addition of coloring or flavoring agents or preservatives to the cells after confluency is reached and prior to harvesting could be performed using the inlet port of the cartridge. This would readily enable agents to efficiently perfuse any void space via the lumens of the hollow fibers.
Conclusion
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 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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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