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 .
Status of the Claims
Claims 1-4, 6-16, and 18-24 are currently pending.
Claims 1-4, 6-16, and 18-24 are currently amended.
Claims 12-16 and 18-24 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 5, and 17 are canceled.
Claims 1-4 and 6-11 have been considered on the merits.
Withdrawn Objections/Rejections
The objections made onto claims 2-11 are withdrawn in light of the amendments submitted on 06/01/2026.
The 112(b) rejections made onto claims 1-11 are withdrawn in light of the amendments made on 06/01/2026.
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 (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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 6-7, and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smith et al (US20140186937A1).
Regarding claim 1, Smith teaches a closed system for the method of culturing cells to form a tissue (Fig. 12a shows closed process).
Regarding claim 1 step a), Smith teaches that the system comprises a cell growth and expansion bioreactor (item 300 chamber of Fig. 12a “Type II” and [0189]). Smith teaches that the system comprises one or more tissue formation reactors as required by claim 1 (item 306 tissue chamber Fig. 12 and [0189]). Smith teaches that “FIG. 12 c illustrates a multi-zone differentiation/tissue formation chamber 306 that comprises up to three implantable differentiation scaffolds 312, all of which may simultaneously proceed toward tissue construct formation. This allows for the preparation of different sizes of implantable tissue and for the use of alternate implantable differentiation scaffolds to assess and maximize tissue yield” ([0192]), therefore Smith meets the newly amended limitations of two or more tissue formation reactors. Further, Smith teaches a manifold system for selectively diverting media and cells from a bioreactor between the two or more tissue formation reactors (see Fig. 17, and Fig. 12c and Fig. 12a). Smith teaches that the system comprises a cell retention device which is a filter (item 316b in Fig. 12 and [0189]).
Regarding claim 1 step c), Smith teaches seeding the cell growth and expansion bioreactor with cells and medium and expanding the cell density within the cell growth and expansion reactor to a desired density as required by claim 1 ([0218]). Smith teaches processing the cells into the tissue formation reactor and removing growth media as required by claim 1 ([0221]). Further, Smith teaches that the cell retention device concentrates the cells and then delivers the cells via the manifold system (Fig. 12, Fig. 17, and [0203]). Smith teaches converting the media in the bioreactor to a differentiation media through the manifold system of Fig. 17/Fig. 12, differentiating and growing the cells in one or more formation reactors until a desired confluency is reached, and harvesting the tissue from the tissue formation reactor as required by claim 1 ([0222]).
Regarding claim 2, Smith teaches that the method is continuous or semi-continuous as required by claim 2 ([0204]/[0206]/[0210]).
Regarding claim 6, Smith teaches that the system further comprises one or more monitoring systems for temperature ([0179]), oxygen ([0179]), carbon dioxide ([0179]), cell density ([0195]), fluid flow ([0187]), and metabolic turnover ([0236]) as required by claim 6.
Regarding claim 7, Smith teaches that the cell retention device can be bypassed (see Fig. 17 chambers 300 and 306 can be directly accessed through the connection points without passing through filter 316C so it meets the limitations of “can be bypassed” of claim 7).
Regarding claim 9, Smith teaches that the tissue can be sterilely harvested from the tissue reactors while maintaining the sterility of the system as required by claim 9 (see claims 83 and 120 of Smith).
Regarding claim 10, Smith teaches that the cells are able to be grown in suspension growth ([0182]), aggregate growth ([0189]), and microcarrier growth ([0191]) as required by claim 10.
Regarding claim 11, Smith teaches that the tissue reactor contains scaffolding for cell attachment as required by claim 11 ([0222]).
Therefore, Smith anticipates the claims.
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 3-4, and 8 remain rejected under 35 U.S.C. 103 as being unpatentable over Smith et al (US20140186937A1), as applied to claims 1-2, 6-7, and 9-11 in the 102 rejection above, and in view of Angelini et al (US11193103B2).
Regarding claims 3-4 and 8, the limitations of the independent claim 1 are taught above.
Smith does teach that the bioreactor can be manufactured in various sizes and configurations as required to support a varying number and size of proliferation and differentiation scaffolds or substrates ([0069]), however Smith does not explicitly teach the size of the cell growth and expansion reactor to be from 0.5 to 20,000 liters as required by claim 3, or from 0.5 to 2,000 liters as required by claim 4. Additionally, Smith does teach that the scaffold used in the growth and expansion reactor can be a fiber filter scaffold, but is silent as to whether this scaffold is a hollow fiber reactor as required by claim 8.
However, Angelini teaches a bioreactor system in which the bioreactor has a volume of at least 2, 3, 10, 35, 50 Liters or more as required by claims 3-4 (Col. 2, para 2). Additionally, Angelini teaches the bioreactor to be a hollow fiber bioreactor as required by claim 8 (col. 18, para 3). Angelini teaches the use of a 15 L capacity bioreactor which employed a hollow fiber bioreactor set up in which Angelini found “the hollow fiber filter retained cells but allowed proteins and nutrients to pass through” (col. 18, para 3). Additionally, Angelini found that in perfusion bioreactors, such as hollow fiber filter perfusion reactors, “The constant addition of fresh medium while eliminating waste products may provide the cells in the cell culture with the nutrients they require to achieve high cell concentrations. Unlike the continually changing conditions during batch and fed-batch cultures, the perfusion method offers the means to achieve and maintain a culture in steady state” (Col. 9, para 2).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the bioreactor system taught by Smith with the specific volume of bioreactor and hollow fiber bioreactor system to arrive at the instant invention. One of ordinary skill in the art would be motivated to make the combination regarding size/volume of the bioreactor because Smith teaches this variable is dependent on the desired outcome ([0069]) and Angelini teaches a wide range of bioreactor volumes which are acceptable (Col. 2, para 2). One of ordinary skill in the art would be motivated to make the combination regarding the hollow fiber reactor system because smith illudes to the use of a fiber filter system and Angelini found that in perfusion bioreactors, such as hollow fiber filter perfusion reactors, “The constant addition of fresh medium while eliminating waste products may provide the cells in the cell culture with the nutrients they require to achieve high cell concentrations. Unlike the continually changing conditions during batch and fed-batch cultures, the perfusion method offers the means to achieve and maintain a culture in steady state” (Col. 9, para 2). One of ordinary skill in the art would have a reasonable expectation of success when combining Smith with Angelini because both teach bioreactor systems with overlapping functions/uses.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 06/01/2026 have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 11, last para spanning pg. 12, para 1-3) that Smith does not teach multiple tissue formation chambers and that Smith does not teach the tube manifold system of the newly amended claim 1.
In response, the argument is not found persuasive. Smith teaches that “FIG. 12 c illustrates a multi-zone differentiation/tissue formation chamber 306 that comprises up to three implantable differentiation scaffolds 312, all of which may simultaneously proceed toward tissue construct formation. This allows for the preparation of different sizes of implantable tissue and for the use of alternate implantable differentiation scaffolds to assess and maximize tissue yield” ([0192]), therefore Smith meets the newly amended limitations of two or more tissue formation reactors. Further, Smith teaches a manifold system for selectively diverting media and cells from a bioreactor between the two or more tissue formation reactors (see Fig. 17, and Fig. 12c and Fig. 12a). Thus, the argument is not found persuasive.
Applicant argues (Remarks, pg. 14, last two para) that smith does not teach the alleged deficiencies which are addressed at point 17 above, and in addition, Applicant argues that Angelini does not cure the alleged deficiencies of Smith and that there is no motivation to combine Smith with Angelini.
In response, the argument is not found persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the bioreactor system taught by Smith with the specific volume of bioreactor and hollow fiber bioreactor system to arrive at the instant invention. One of ordinary skill in the art would be motivated to make the combination regarding size/volume of the bioreactor because Smith teaches this variable is dependent on the desired outcome ([0069]) and Angelini teaches a wide range of bioreactor volumes which are acceptable (Col. 2, para 2). One of ordinary skill in the art would be motivated to make the combination regarding the hollow fiber reactor system because smith illudes to the use of a fiber filter system and Angelini found that in perfusion bioreactors, such as hollow fiber filter perfusion reactors, “The constant addition of fresh medium while eliminating waste products may provide the cells in the cell culture with the nutrients they require to achieve high cell concentrations. Unlike the continually changing conditions during batch and fed-batch cultures, the perfusion method offers the means to achieve and maintain a culture in steady state” (Col. 9, para 2). One of ordinary skill in the art would have a reasonable expectation of success when combining Smith with Angelini because both teach bioreactor systems with overlapping functions/uses. Thus, the argument is not found persuasive.
Conclusion
No claims are allowed.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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