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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11, in the reply filed on 11/17/2025 is acknowledged.
Claims 12-24 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/17/2025.
Status of the Claims
Claims 1-24 are currently pending.
Claims 12-24 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 1-11 have been considered on the merits.
Claim Objections
Claims 2-11 is objected to because of the following informalities: “The process of Claim” in the preamble of each claim should not be capitalized. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the phrase “seeding said cell growth and expansion reactor” in line 5, which is indefinite. It is not clear what is being seeded in the cell growth and expansion reactor. Appropriate clarification is required.
Claim 1 recites the limitation "the cell density" in line 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the cells" multiple times throughout lines 7, 8, and 12. There is insufficient antecedent basis for this limitation in the claim.
Claims 1 and 10 recites the limitation "the bioreactor" in lines 9-10 and 1, respectively. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the phrase “converting the bioreactor to a differentiation media reservoir” in lines 9-10, which is indefinite. It is unclear what is meant by converting a bioreactor to a media reservoir. It is not clear if the physical bioreactor chamber is somehow altered to no longer perform bioreactions and rather its function becomes a media reservoir or if the media within the bioreactor is changed out for a differentiation medium, however the bioreactor remains the functional bioreactor in the system. Appropriate clarification is required.
Claims 2 and 5 recites the limitation "process system" in lines 1 and 2, respectively. There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites the limitation “further comprising a manifold system to integrate said tissue formation reactors if said process system has two or more of said tissue formation reactors”, which is indefinite. It is unclear if the limitation of “further comprising a manifold system” is required if the process system does not contain two or more tissue formation reactors. Appropriate clarification is required.
Claim 10 recites the limitation "the cells" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the phrase “wherein the cells in the bioreactor are adapted to suspension growth, aggregate growth, or microcarrier growth”, which is indefinite. It is unclear what the term “adapted to” does to limit the claimed cells. It is not clear if certain cell types are adapted to a specific type of growth or whether a cell type needs to be actively grown by a certain method to be “adapted to” the method of growth. For example, are any cells grown in suspension considered “adapted to suspension growth”? Appropriate clarification is required.
Dependent claims 3-4, 6-9, and 11 are included in this rejection for being dependent on a rejected claim.
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, 5-7, 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 process of culturing cells to form a tissue (Fig. 12a shows closed process). Smith teaches that the system comprises a cell growth and expansion reactor as required by claim 1 (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. 12a “Type II” and [0189]). Smith teaches that the system comprises a cell retention device which is a filter as required by claim 1 (item 316b in Fig. 12 and [0189]). Smith teaches seeding the cell growth and expansion reactor 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]). Smith teaches converting the media in the bioreactor to a differentiation media, 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]). Smith teaches that the process is continuous or semi-continuous as required by claim 2 ([0204]/[0206]/[0210]). Smith teaches that the system further comprises a manifold tube system which connects the system to different/various reactors as required by claim 5 (Fig. 17, items 316 a-d depict a tube system connecting different reactors). 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. Smith teaches that the cell retention device can be bypassed as required by claim 7 (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). 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). 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. 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 1, 3-4, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al (US20140186937A1), 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.
Conclusion
No claims are allowed.
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
/ANOOP K SINGH/Primary Examiner, Art Unit 1632