DETAILED ACTION
This action is in reply to papers filed 12/31/2025.
Claims 1-12 and 25 are pending and examined herein. Claim 25 is new.
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 elected without traverse Group I, drawn to claims 1-12, in the reply filed on 04/29/2025. New claim 25 is examined as part of Group I.
Claims 13-23 are withdrawn from consideration as being drawn to a nonelected invention.
Withdrawn Objection(s) and Rejection(s)/Response to Arguments
The objections to claims 1-12 are withdrawn in light of the amendments to the claims.
The rejection of claims 1-4, 6, 8, and 12 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 2003/0036192 A1 (Singh) is withdrawn in light of the new limitation to amended claim 1, which requires “removing and filtering the fluid medium from the bioreactor at a flow rate of 5 to 10 mL/mins, 10 to 15 mL/mins, or 20 to 25 mL/mins to minimize cell loss” (lines 5-6).
The rejection of claims 1-3, 9, and 12 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 2016/0355774 A1 (Konishi) is withdrawn in light of the new limitation to amended claim 1 regarding flow rate (lines 5-6).
The rejection of claims 1 and 5 under 35 U.S.C. 103 over US 2003/0036192 A1 (Singh) is withdrawn in light of the new limitation to amended claim 1 regarding flow rate (lines 5-6).
The rejection of claims 1 and 7 under 35 U.S.C. 103 over US 2003/0036192 A1 (Singh), in view of OriGen Biomedical (pamphlet for PermaLifeTM Cell Culture Bags, 2017) is withdrawn in light of the new limitation to amended claim 1 regarding flow rate (lines 5-6).
The rejection of claims 1 and 10-11 under 35 U.S.C. 103 over US 2016/0355774 A1 (Konishi), in view of WO 2008/117195 A2 (Merkle) and US 2020/0306299 A9 (Roy; correction of US 2019/0343879 A1 published 11/14/2019) is withdrawn in light of the new limitation to amended claim 1 regarding flow rate (lines 5-6).
Claim Objections
Claim 10 is objected to because of the following informalities: The phrase “to inhibits loss of” should be corrected to “to inhibit loss of” (line 9). Appropriate correction is required.
Claim Interpretation
Claim 1 recites the phrase “for purifying a cellular population” in the preamble (line 1). If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). See MPEP 2111.02(II).
Claim 7 recites the phrase “for cryogenic storage” (lines 2-3), which is an intended use of the flexible bag vessels (line 2). The intended use does not impose additional limitations to the method as claimed, and therefore is not given patentable weight. See MPEP 2111.02(II).
Claim Rejections - 35 USC § 112(b)
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 1-12, and 25 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, as amended, recites the limitation “removing and filtering the fluid medium from the bioreactor at a flow rate of 5 to 10 mL/mins, 10 to 15 mL/mins, or 20 to 25 mL/mins” (lines 8-9). The limitation “mL/mins” implies that “mL per minute” (i.e., mL/1 min). However, the claim recites “mins” in the plural, implying that the limitation “mL/mins” refers to “mL per [undefined number of] minutes.” Example No. 1 of the specification recites “The flow rates included a first flow rate at 5 to 10 mL/mins, an intermediate flow rate of 10 to 15 mL/mins and a high flow rate of 20 to 25 mL/mins” (p 43, para 168), and thus, the specification does not offer further guidance on which interpretation should be given to claim 1. Therefore, the metes and bounds of claim 1 are unclear. For the sake of compact prosecution, the limitation “mL/mins” is interpreted as “mL/min.” Claims 2-9, 12, and 25 are included in the rejection because they depend from claim 1.
Claim 10, as amended, recites the limitation “removing and filtering the fluid medium from the bioreactor at a flow rate of 5 to 10 mL/mins, 10 to 15 mL/mins, or 20 to 25 mL/mins to inhibits [sic] loss of desired cells, the fluid medium being filtered through a filter apparatus comprising a filter member, the filter member having a pore size that inhibits the desired cells from being withdrawn from the bioreactor as the fluid medium is withdrawn and allows the second type of the biological cells to pass through the filter member” (lines 8-13; emphases added). It is unclear what “desired cells” (lines 8 and 11) refer to in the claim. As written, “desired cells” may refer to either the first type of biological cells, the second type of biological cells, or a third, hitherto undefined type of biological cells. The possibility for multiple interpretations renders the metes and bounds of the claim indefinite, as a filter member having a pore size that inhibits the first type of biological cells, which are bound to microcarriers, from being withdrawn from the bioreactor, would be structurally different from a filter member having a pore size that inhibits the second type of biological cells, which are not bound to microcarriers. Based on the contents of the disclosure (e.g., Fig. 18; p 35, para 140 – p 37, para 143), and the previous iteration of claim 10, “desired cells” is interpreted as “the first type of biological cells bound to microcarriers.” Claim 11 is included in the rejection because it depends from claim 10.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
From M.P.E.P. § 2163, the analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.
For claims drawn to a genus, possession may be shown (for example) through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
Claim 25 is drawn to the method of claim 1, wherein the removing and filtering causes less than 2% cell loss within the bioreactor. The method of claim 25 recites a structure: a bioreactor comprising a filter apparatus, which comprises a filter member, as recited in claim 1, which is required to carry out the method of claim 25. The method of claim 25 also recites a function: wherein the removing and filtering causes less than 2% cell loss within the bioreactor. Thus, claim 25 is drawn to a method comprising the use of a very large genus of a bioreactor comprising a filter apparatus, which comprises a filter member, comprising the claimed function.
Neither the specification nor the prior art establishes a structure-function relationship wherein a bioreactor comprising a filter apparatus, which comprises a filter member, as recited in claim 1, would be capable of functioning as claimed in claim 25 with any degree of predictability.
The instant specification appears to only have the following bioreactor comprising a filter apparatus, which comprises a filter member, capable of functioning according to claim 25: a 1 liter stirred-tank bioreactor comprising a filter apparatus comprising a filter member, wherein the filter apparatus is similar to the design illustrated in Fig. 4A, and wherein the filter member has a length of approximately 1.5 in2 and the exterior surface of the filter member had a surface area of 0.65 in2, the filter member has an absolute pore size of 3-4 microns, and a tubular member attached to the filter member has an inside diameter of 6.35 mm (p 42, para 166-168). The breadth of the bioreactor comprising a filter apparatus, which comprises a filter member, encompassed in claim 1 is broad. For example, the filter apparatuses illustrated in Fig. 1-3, 4B-C, and Fig 5, are also encompassed by claim 1. However, the specification does not disclose that the use of a filter apparatus similar to the design illustrated in Fig. 1-3, 4B-C, or Fig 5 results in the claimed function of claim 25. The specification further discloses that the process of the disclosure can be carried out with less than 10% total cell loss (para 162), less than 10% cell loss is a wider range than the specific range of 2%, as recited in claim 25. Thus, the specification does not disclose any other embodiments, aside from the embodiment recited in para 166-168, which would be encompassed within pending claim 25. Furthermore, the specification does not identify what changes in design, structure, etc. could be made to the bioreactor comprising a filter apparatus, which comprises a filter member, and that would be encompassed by the structural limitations of claim 1, and would predictably result in the claimed function of claim 25. As such, the instant specification does not provide a sufficient representative sampling of bioreactors comprising a filter apparatus, which comprises a filter member that are capable of providing for said function as claimed in claim 25.
The prior art is unpredictable. Goudar (US 2017/0114381 A1) teaches a method for a perfusion cell culture system, wherein the method comprises the use of a bioreactor comprising a filter apparatus, which comprises a filter member, and wherein the flow rate taught therein can be optimized to arrive at the method of claim 1 (see rejection of claim 1 under 35 USC 103 over Goudar, below). However, although the bioreactor system taught in Goudar reads on the bioreactor and filtering system as recited in claim 1, and the perfusion method taught therein renders obvious the method of claim 1, Goudar does not teach that the filtering method taught therein causes less than 2% cell loss in the bioreactor, as recited in claim 25. Thus, the prior art cannot be relied upon for making up for the deficit of the instant specification with regard to a sufficient representative number of species of bioreactors comprising a filter apparatus, which comprises a filter member, that provide for said function as claimed.
Accordingly, neither the specification nor the prior art establishes a known structure-function relationship wherein the genus of bioreactors comprising a filter apparatus, which comprises a filter member, as recited in claim 1 and required out to carry out the method of claim 25, is capable of providing for the function as claimed in claim 25 with any predictability. In this case, the skilled artisan would not have reasonable concluded at the time of the invention that application was in possession of the invention as claimed.
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.
Claim(s) 1-5, 8, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Goudar (US 2017/0114381 A1; cited in IDS 04/20/2022).
Regarding claim 1: Goudar teaches a method for a perfusion cell culture system (Example 2, para 197-211). Goudar teaches inoculating a CHO cell line into 2 L bioreactors at a density of 2×106 viable cells/mL in a working volume of 1500 mL of a serum-free chemically-defined perfusion medium (reads on fluid medium) (para 198). Goudar teaches initiating the cell culture runs in batch mode, and starting perfusion on day 2 using an alternating tangential flow perfusion and filtration system (para 198). Goudar teaches that the cell culture was continuously circulated through the lumen side (inside; see para 129) of an external vertically oriented filter, entering at the upper end, and that permeate (reads on fluid medium) was continuously withdrawn via peristaltic pump (para 199) (reads on removing and filtering the fluid medium from the bioreactor).
The bioreactors were equipped with either 30 kDa or 750 kDa hollow fiber filters (para 199). Goudar teaches that hollow fiber filters with a molecular weight cut off of 500 kDa or more allow protein to pass through into the permeate, whereas hollow fiber filters with a molecular weight cut off of 300 kDa or less can be used to retain the desired protein in the retentate and return it back to the bioreactor (para 129). Goudar teaches that 30 kDa and 750 kDa hollow fiber filters are used to collect harvest permeates (para 187-188), which refers to a process to retain cells in the culture while allowing proteins to pass into the permeate (para 127); that is, neither either 30 kDa or 750 kDa hollow fiber filters allows for the passage of cells.
Goudar teaches that perfusion culture, such as the one disclosed in Example 2 (para 197-211), is one in which the cell culture receives the addition of fresh medium (reads on adding to the biological cell population a buffer medium) and spent medium is removed from the bioreactor (para 126).
Goudar teaches that the perfusion rate, defined as “the amount of media that is passed through (added and removed) from a bioreactor, typically expressed as some portion of or a multiple of the working volume, in a given time” (para 126) (reads on flow rate), increased from 0.5 to 3 mL/minute over the cell culture run in Example 2 (para 200). Goudar further teaches that perfusion rates can be less than a working volume to many working volumes per day, wherein “working volume” refers to the amount of bioreactor volume used for cell culture (para 126). Goudar does not teach a flow rate of 5 to 10 mL/mins, 10 to 15 mL/mins, or 20 to 25 mL/mins, as recited in claim 1.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have optimized the flow rate based on factors such as the type of cell used, size of hollow fiber filters, and size of bioreactor, to arrive at the claimed invention. Routine optimization is not considered inventive and no evidence has been presented that increasing the flow rate from 3 mL/minute, as taught by Goudar, to 5 mL/min, as claimed, was other than routine, that the flow rate resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. As noted in In re Aller, 105 USPQ 233 at 235, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Therefore, Goudar renders obvious the method of claim 1.
Regarding claim 2: Goudar teaches that perfusion culture, such as the one disclosed in Example 2 (para 197-211), is one in which spent medium (reads on fluid medium containing biological byproducts) is removed from the bioreactor (para 126, 129), indicating that the filter member has a pore size that permits passage of the spent medium for removal from the bioreactor.
Regarding claims 3-4: Goudar teaches that the working volume, which refers to the amount of bioreactor volume used for cell culture (para 126), in Example 2 was 1500 mL (claim 4). Goudar teaches that the perfusion rate, defined as “the amount of media that is passed through (added and removed) from a bioreactor” (para 126), increased from 0.5 to 3 mL/minute over the cell culture run in Example 2 (para 200). Goudar teaches that permeate samples were collected at the same rate as the perfusion rate, and that samples were taken once daily from the bioreactor and the permeate line (para 200), and that samples were analyzed until at least Day 6 for reactors with 750 kDa filters, and at least until Day 14 for reactors with 30 kDa filters (para 201). Assuming the most conservative parameters, with a rate of 0.5 mL/minute and 6 days of perfusion culture, this would amount to 4320 mL of medium perfused, which is greater than 50% of the starting working volume of 1500 mL (claim 3).
Regarding claim 5: Goudar does not teach repeating the process in Example 2 from about 2 cycles to about 5 cycles. Goudar teaches a different experimental example for extended periodic cell culture process (Example 1), wherein the perfusion process was repeated until the culture was terminated (para 180).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have optimized number of cycles based on factors such as the working volume of the perfusion culture, to arrive at the claimed invention. As noted in In re Aller, 105 USPQ 233 at 235, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Regarding claim 8: Following the discussion of claim 1, the filter members used in Example 2 of Goudar had a pore size of either 30 kDa or 750 kDa (para 199). Example 2 of Goudar does not teach a filter member with absolute pore size of from about 1 micron to 9 microns.
Gouar teaches that hollow fibers for microfiltration typically have a pore size ranging from 0.1 μm to 5-10 μm (para 129). Goudar teaches that depending on the pore size or molecular weight cutoff of the hollow fiber material, cell culture components including cell culture media, cells (whole and lysed), soluble expressed recombinant proteins, host cell proteins, and waste products are retained on the lumen side (inside) or passed through the filter (para 129).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the filter member used in Example 2 of Goudar with a filter member with a pore size ranging from 5-10 μm, as taught in Goudar (para 129). One of ordinary skill in the art would have been motivated to make this modification to retain certain cell culture components during microfiltration, as taught in Goudar. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Goudar teaches that a filter member with a pore size ranging from 5-10 μm can be used for microfiltration.
Regarding claim 12: Goudar teaches that the perfusion in Example 2 was performed using an alternating tangential flow perfusion and filtration system (para 198), which is a continuous perfusion system.
Claim(s) 1 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Goudar (US 2017/0114381 A1), in view of in view of OriGen Biomedical (pamphlet for PermaLifeTM Cell Culture Bags, 2017).
The teachings of Goudar are set forth above. Goudar anticipates claim 1.
Regarding claim 7: Following the discussion, Goudar teaches in Example 2 that samples comprising cells were taken once daily from the bioreactor (para 200). Goudar does not teach a step of dispensing the biological cell population and buffer medium into flexible bag vessels.
OriGen Biomedical teaches cell culture bags that can be used to protect, store, and freeze critical cell cultures (p 1, para 1). The bags are made of inert FEP (fluorinated ethylene propylene; p 1, para 1) and are flexible (p 1, para 4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Goudar by dispensing the biological cell population and buffer medium into flexible bag vessels, as taught by OriGen Biomedical. One of ordinary skill in the art would have been motivated to make this modification to protect, store, and freeze critical cell cultures, as taught by OriGen Biomedical. One of ordinary skill in the art would have had a reasonable expectation of making this modification because OriGen Biomedical teaches that cell cultures can be stored in the cell culture bags disclosed therein.
Claim(s) 10 is rejected under 35 U.S.C. 103 as being unpatentable over Goudar (US 2017/0114381 A1), in view of WO 2008/117195 A2 (hereinafter Merkle).
The teachings of Goudar are set forth above.
Goudar anticipates the method of claim 1, as set forth above. Claim 10 differs from claim 1 in adding microcarriers to the bioreactor to bind the microcarriers to a first type of the cells and not a second type of the biological cells.
Goudar teaches that microcarriers may be used with bioreactor systems taught therein (para 142). However, Goudar does not exemplify or reduce to practice the use of a microcarrier.
Merkle teaches a method for isolating cells using microcarrier beads (Abstract, Fig. 4). Merkle teaches that the microcarriers beads may be contacted with cells in culture, such that the cells associate with the microcarrier beads during growth (p 3, in 14-16). Merkle teaches functionalizing the surface of the microcarrier bead, such that only a certain cell type adheres to the microcarrier bead, which allows for the selective isolation of said cell types from a mixed population (p 10, ln 6-9). The surface of the microcarrier may be modified with a specific antibody or adhesion molecule, such that only a singular cellular species from a mixed cell population will bind to the microcarrier bead (p 10, ln 12-15; Fig 1). Once the cells grow on the surface of the microcarrier beads, the beads bearing the cells can be isolated by filtering (p 9, ln 29-31).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Goudar by using microcarriers that bind to a subset of cells, as taught in Merkle. One of ordinary skill in the art would have been motivated to make this modification to select and isolate desired cells from a mixed cell population, as taught in Merkle. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Goudar teaches that microcarriers may be used with bioreactor systems taught therein.
Claim(s) 1, 6, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Goudar (US 2017/0114381 A1), in view of WO 2008/117195 A2 (hereinafter Merkle) and US 2020/0306299 A9 (hereinafter Roy).
Goudar renders obvious claim 1.
Goudar, in view of Merkle, renders obvious claim 10.
Regarding claims 6 and 11: Following the discussion of claim 10, Merkle teaches the use of microcarrier beads coated with the vascular cell adhesion molecule-1 (VCAM-1) to separate white blood cells, which comprise T cells and NK cells, from plasma (p 11, ln 21-27). T cells and NK cells are species of white blood cells. Goudar, in view of Merkle, does not teach the method of claim 10, wherein the first or second cells comprise T cells or NK cells specifically.
Roy teaches the use of 3D microcarriers to culture and expand suspension cells, including T cells in a bioreactor (para 3, 19). Roy teaches that T cells are useful for immunotherapy, such as CAR-T cell therapy (para 4-9).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Goudar, in view of Merkle, by using microcarriers to isolate T cells. One of ordinary skill in the art would have been motivated to make this modification because Roy teaches that T cells are useful for immunotherapy. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Goudar teaches that mammalian cells in suspension can be cultured in the cell culturing system taught therein (para 102), and human T cells are mammalian suspension cells. Furthermore, Merkle teaches that the microcarrier beads taught therein can be used to separate white blood cells (p 11, ln 21-27), and T cells are a species of white blood cells.
Claim(s) 1-3, 9, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0355774 A1 (hereinafter Konishi).
Konishi teaches a cell culturing system that allows for the removing of culture medium from the culture tank (Abstract; para 6; Fig 1). The cell culture system (Fig 1: 1) comprises a cell culturing device (Fig 2-4: 5) (reads on bioreactor), which comprises a culture tank (Fig 2-4: 15), a shaft member (Fig 2-4: 17), and a filter (Fig 2-4: 21) (para 49).
The culture tank (15) stores culture solution in which the cells are cultured and grown (para 50) (reads on expanding a biological cell population in a fluid medium of claim 1). The cells may be suspension cells (para 39) (reads on unsupported cells of claim 1).
The filter (21) allows the culture solution, but not cells, to pass through (para 6, 58) (claim 1). Metabolites produced from the cells (reads on biological byproducts) may be present in the culture solution removed from the culture tank (para 67) (claim 2).
A culture solution tank (Fig 1: 3; Fig 7-8: 3A) feeds fresh solution (reads on buffer medium) to the culture tank via a feed circuit (Fig 1, 7: 7-8; Fig 8: 7A-8A) (para 67) (claim 1).
The shaft member (17) is a hollow tubular member (para 52) with a first end defining a first opening (Fig 4: 17a) and a second end defining a second opening (Fig 4: 17b) (claim 9). The second end of the shaft member (Fig 4: 17b) is inserted into the filter member (Fig 4: 21), such that the filter completely surrounds and encloses the second opening (Fig 4; para 58) (claim 9).
In Example 1, Konishi discloses seeding 2x107 human iPS cells in 100 mL of culture solution in a culture tank, resulting in a density of 2x105 cells/mL (para 97). The solution volume in the culture tank was maintained substantially at the same level during culturing (para 104). At the end of the experiment, the number of cells was 2x108 (Table 1) in approximately 100mL of culture solution (para 104), which is a density of approximately 2x106 cells/mL (claim 1).
In Example 1, Konishi discloses that 100 mL/day of culture solution was circulated on day 1, which is 100% of the volume of the culture solution (para 104) (claim 3). Konishi discloses that the culture solution was continuously perfused from day 1 to day 6 of culture (para 104) (claim 12).
Regarding the flow rate in claim 1: In Example 1, Konishi teaches that circulation speed (reads on flow rate) was 100 mL/day on Day 1, 200 mL/day on Day 2, 400 mL/day on Day 3, and 600 mL/day on and subsequent to Day 4 (para 104). Flow rate of 600 mL/day is 0.42 mL/min. Konishi does not teach a flow rate of 5 to 10 mL/mins, 10 to 15 mL/mins, or 20 to 25 mL/mins, as recited in claim 1.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have optimized the flow rate based on factors such as the type of cell used, size of hollow fiber filters, and size of bioreactor, to arrive at the claimed invention. Routine optimization is not considered inventive and no evidence has been presented that increasing the flow rate from 0.42 mL/minute, as taught by Konishi, to 5 mL/min, as claimed, was other than routine, that the flow rate resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. As noted in In re Aller, 105 USPQ 233 at 235, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
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 Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RISA TAKENAKA/Examiner, Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
Prosecution Insights