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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/17/2026 has been entered.
Claim Status
1. The amendment filed 02/17/2026 has been entered. Claims 1, 6, 7, and 8 remain pending and are under consideration.
Priority
2. Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119 (a)-(d).
The certified copy has been filed in parent Application No. JP2018-166843, filed on 9/06/2018.
3. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior
to declaration of an interference, a certified English translation of the foreign application must be
submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-
English application.
Withdrawn Claim Objections and Rejections
4. The objection of claim 1 is withdrawn in view of Applicant’s amendment to the claim.
5. The objection of claim 7 is withdrawn in view of Applicant’s amendment to the claim.
6. The objection of claim 8 is withdrawn in view of Applicant’s amendment to the claim.
Claim Interpretation
7. For the purpose of applying prior art, “consisting essentially of” of claims 1, 7, and 8 is interpreted as “comprising” for searching and applying prior art because there is no clear indication in the specification or claims of what would affect the ammonia adsorption ability of L-type zeolite (see MPEP 2111.03 (III)).
8. For the purpose of applying prior art, claim 1 is interpreted as the ammonia adsorbent comprises any L-type zeolite but is not limited to only L-type zeolite and adsorbs a maximum of 32% of the glucose present in the culture solution but can adsorb anything less than 32% including not adsorbing glucose (0%).
9. For the purpose of applying prior art, claim 7 is interpreted as the ammonia adsorbent that comprises L-type zeolite and any additional components that can adsorb ammonia and a concentration of ammonia adsorbent of between 0.025 g/mL and 0.1 g/mL is achieved by any module that can house any amount of ammonia adsorbent and a culture vessel that can house any volume of culture solution such that dividing the amount of ammonia adsorbent by the volume of culture solution results in a concentration between 0.025 g/mL and 0.1 g/mL.
10. For the purpose of applying prior art, claim 8 is interpreted as the ammonia adsorbent comprises L-type zeolite and any additional components that can adsorb ammonia and a concentration of ammonia adsorbent of between 0.025 g/mL and 0.1 g/mL is achieved by any module that can house any amount of ammonia adsorbent and a culture vessel that can house any volume of culture solution such that when a volume of culture solution contacts an amount of ammonia adsorbent by circulation, dividing the amount of ammonia adsorbent by the volume of culture solution results in a concentration between 0.025 g/mL and 0.1 g/mL.
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.
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.
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.
11. Claim(s) 1 and 6 remain rejected under 35 U.S.C. 103 as being unpatentable over Nayve (Nayve FR et. al. Cytotechnology. 1991 Jun;6(2):121-30; previously cited), hereinafter Nayve in view of Insuwan (Insuwan, Wilaiporn, et. al. Journal of Porous Materials 21.3 (2014): 345-354; previously cited), hereinafter Insuwan as evidenced by Calzaferri (Calzaferri, Gion, et al. Comptes Rendus Chimie 9.2 (2006): 214-225; previously cited), hereinafter Calzaferri in view of Kondo (JP-03119970-A; previously cited), hereinafter Kondo. A machine translation of JP-03119970-A was previously provided. The translation was performed on October 21, 2024 of pages 1 – 4 of the original document.
Regarding “ammonia adsorbent” and “wherein the ammonia adsorbent contacts with a solution containing ammonia and glucose to adsorb ammonia in the solution” and “wherein the solution is a culture solution of cells or microorganisms” of claim 1, Nayve teaches synthetic zeolite A-3 in contact with a solution containing ammonia and glucose (E-RDF medium) and cells to adsorb ammonia (page 122, right col. para. 2 – 3; page 123, left col. para. 2 and right col. para. 2 – 3; page 124, left col. para. 1; Figure 1; Figure 5 and 6).
Regarding “wherein the ammonia adsorbent adsorbs 32% glucose at maximum” of claim 1, Nayve teaches the glucose concentration in the culture solution remained high after contacting the zeolite (page 126, right col. para. 2). Nayve teaches in Figure 5 and 6 that the concentration of glucose increases after beginning ammonia removal whereas at the same timepoint, ammonia decreases (Figure 5, compare 50 h to 70 h; Figure 6, compare ~70 h to ~90 h). Nayve teaches glucose concentrations in the medium remained about 3 mmol/l after the start of perfusion (page 128, left col. para. 1).
Regarding claim 6, Nayve teaches removing ammonia by bringing zeolite A-3 into contact with ammonia (page 124, left col. para. 1 and right col. para. 2; Table 1).
Nayve does not teach “L-type zeolite” or “wherein an amount of the L-type zeolite in the solution is between 0.025 g/mL and 0.1 g/mL” of claim 1. However, Nayve teaches 200 mL of packed zeolite A-3 beads for removal of ammonia from culture broth in Figure 1 with a working volume of 250 mL of culture (page 122, right col. last para.; Figure 1; page 123, left col. para. 2). Nayve teaches both natural and synthetic zeolites can adsorb ammonia similarly as shown in Table 1 (page 124, right col. para. 2). Nayve teaches there is a pressing necessity to develop a system for the reduction, if not the removal of toxic metabolites such as ammonia from animal cell culture systems (page 121, left col. and right col. para. 1). Nayve teaches adsorption is an attractive alternative to physically remove accumulated metabolites from culture broth (page 122, left col. para. 2). Nayve teaches mouse-mouse hybridoma TO-405 cells have been reported to be especially susceptible to ammonia inhibition in serum-free medium (page 122, left col. last para.). Nayve teaches ammonia removal with zeolite maintained cell viability above 90% and ammonia was effectively maintained below the inhibitory level (page 126, right col. para. 2). Nayve teaches packed zeolite A-3 beads can selectively and effectively remove ammonia from the broth of hybridoma cell cultures and could also mean high MAb production (page 129, left col. para. 2).
Regarding “L-type zeolite” of claim 1, Insuwan teaches zeolite L adsorbs ammonia (page 346, left col. para. 3 and right col. para. 1; page 347, right col. para. 2; Figure 3; Table 2). Insuwan teaches zeolite L has ion exchange properties as the H form of zeolite L (H-LTL) was prepared by ion exchange of the K form of zeolite L (K-LTL) with ammonium nitrate resulting in ammonium-bound zeolite L (NH4-LTL) which was subsequently calcined to decompose NH4+ to NH3 (page 346, left col. para. 2). Insuwan teaches zeolite L adsorbs the dye AF and the lone pair of electrons of the amino group of AF interacts with zeolite L via hydrogen bonding (page 351, right col. para. 3; Scheme 1). Insuwan teaches it is possible that the acidic sites on zeolite L donate a proton to the amino group of AF to form -NH3+ which would be attracted to anionic sites of zeolite frameworks (page 351, right col. para. 3). Therefore, Insuwan teaches zeolite L adsorbs ammonia. Because zeolite L of Insuwan and zeolite A of Nayve are chemically very similar and only differ in geometrical properties as evidenced by Calzaferri (page 216, left col. last para.; Figure 2), and Nayve teaches 5 zeolites (natural and synthetic) that can adsorb similar amounts of ammonia (Table 1), one would have been motivated to combine the teachings of Nayve regarding an ammonia adsorbent that is a zeolite A with the teachings of Insuwan regarding an ammonia adsorbent that is zeolite L because both zeolites have similar chemical compositions and both can adsorb ammonia. Insuwan does not teach “wherein an amount of the L-type zeolite in the solution is between 0.025 g/mL and 0.1 g/mL” of claim 1.
Kondo teaches an ammonia adsorbent that includes any substance that adsorbs ammonia including ion exchange resin and addition of the ammonia adsorbent to a culture solution of cells where the ammonia adsorbent can efficiently adsorb ammonia (page 2, lines 27 – 30). Kondo teaches the ammonia adsorbent may be any substance that adsorbs ammonia where the added ammonia adsorbent is 0.1 to 20% added to the culture of the organism (page 2, lines 31 – 34). As Kondo teaches a range of percentages of ammonia adsorbent added to a culture and Nayve teaches 250 mL of culture media, Kondo and Nayve teach an ammonia adsorbent in solution is between 0.025 g/mL and 0.1 g/mL when the percent of adsorbent is 10% (250 mL * 10% = 25 g ammonia adsorbent; 25 g/250 mL = 0.1 g/mL). Additionally, it would be obvious to adjust the concentration, since it is a result-effective variable dependent on amount of ammonia desired to be absorbed and the culture conditions.
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Nayve regarding a zeolite A ammonia adsorbent and method of removing ammonia by contacting ammonia with the zeolite A with the teachings of Insuwan regarding zeolite L adsorbs ammonia and has ion exchange properties with the teachings of Kondo regarding an ammonia adsorbent can be an ion exchange resin that removes ammonia by contacting the adsorbent with ammonia in a culture of cells to arrive at the claimed ammonia adsorbent and method for removing ammonia where the ammonia adsorbent comprises zeolite A and an L-type zeolite in contact with a solution containing ammonia and glucose to adsorb ammonia wherein the ammonia adsorbent adsorbs 32% glucose at maximum wherein the L-type zeolite in is between 0.025 g/mL and 0.1 g/mL and wherein the solution is a culture solution of cells and microorganisms. One would have been motivated to combine the teachings of Nayve, Insuwan, and Kondo to remove ammonia from cell cultures because Nayve teaches there is a pressing necessity to develop a system for the reduction, if not the removal of toxic metabolites such as ammonia from cell culture systems and adsorption is an attractive alternative to physically remove accumulated metabolites from culture broth. One would have a reasonable expectation of success in combining the teachings as Nayve teaches ammonia removal with zeolite maintained cell viability above 90% and ammonia was effectively maintained below the inhibitory level, Insuwan teaches zeolite L adsorbs ammonia and has ion exchange capacity and Kondo teaches the ammonia adsorbent may be an ion exchange resin that adsorbs ammonia.
12. Claim(s) 7 remains rejected under 35 U.S.C. 103 as being unpatentable over Nayve (Nayve FR et. al. Cytotechnology. 1991 Jun;6(2):121-30; previously cited), hereinafter Nayve in view of Insuwan (Insuwan, Wilaiporn, et. al. Journal of Porous Materials 21.3 (2014): 345-354; previously cited), hereinafter Insuwan as evidenced by Calzaferri (Calzaferri, Gion, et al. Comptes Rendus Chimie 9.2 (2006): 214-225; previously cited), hereinafter Calzaferri in view of Kondo (JP-03119970-A; previously cited), hereinafter Kondo. A machine translation of JP-03119970-A was previously provided. The translation was performed on October 21, 2024 of pages 1 – 4 of the original document.
Regarding “a culture vessel housing cells or microorganisms and a culture solution of the cells or the microorganisms”, Nayve teaches in Figure 1 a bioreactor (page 122, right col. last para.).
Regarding “an adsorption module having an ammonia adsorbent”, Nayve teaches in Figure 1 zeolite packed beads for ammonia removal (page 123, left col. para. 2).
Regarding “a circulation path connecting the culture vessel and the adsorption module so as to allow the culture solution separated from the cells or the microorganisms to circulate between the culture vessel and the adsorption module to bring the culture solution into contact with the ammonia adsorbent”, Nayve teaches in Figure 1a circulation path and a peristaltic pump for circulation of cell-free culture broth into the packed zeolite for ammonia removal (page 123, left col.; page 124, left col. para. 1).
Regarding “wherein the culture solution contains ammonia and glucose”, Nayve teaches E-RDF culture broth containing ammonia (page 122, right col. para. 3; Figure 5 and 6).
Regarding “wherein the ammonia adsorbent includes: at least one substance selected from the group consisting of L-type zeolite”, Nayve teaches zeolite A-3 (Figure 1) but does not teach “L-type zeolite”.
Regarding “wherein an amount of the L-type zeolite in the culture solution is between 0.025 g/mL and 0.1 g/mL” and “wherein the amount of the L-type zeolite in the culture solution is an amount of the ammonia adsorbent relative to an amount of the culture solution adapted to be housed in the adsorption module packed with the ammonia adsorbent”, Nayve teaches 200 mL of packed zeolite A-3 beads for removal of ammonia from culture broth in Figure 1 with a working volume of 250 mL of culture (page 122, right col. last para.; Figure 1; page 123, left col. para. 2) but does not teach the recited concentration range.
Nayve does not teach “L-type zeolite” or “wherein an amount of the L-type zeolite in the culture solution is between 0.025 g/mL and 0.1 g/mL”. However, Nayve teaches 200 mL of packed zeolite A-3 beads for removal of ammonia from culture broth in Figure 1 with a working volume of 250 mL of culture (page 122, right col. last para.; Figure 1; page 123, left col. para. 2). Nayve teaches both natural and synthetic zeolites can adsorb ammonia similarly as shown in Table 1 (page 124, right col. para. 2). Nayve teaches there is a pressing necessity to develop a system for the reduction, if not the removal of toxic metabolites such as ammonia from animal cell culture systems (page 121, left col. and right col. para. 1). Nayve teaches adsorption is an attractive alternative to physically remove accumulated metabolites from culture broth (page 122, left col. para. 2). Nayve teaches mouse-mouse hybridoma TO-405 cells have been reported to be especially susceptible to ammonia inhibition in serum-free medium (page 122, left col. last para.). Nayve teaches ammonia removal with zeolite maintained cell viability above 90% and ammonia was effectively maintained below the inhibitory level (page 126, right col. para. 2). Nayve teaches packed zeolite A-3 beads can selectively and effectively remove ammonia from the broth of hybridoma cell cultures and could also mean high MAb production (page 129, left col. para. 2).
Regarding “L-type zeolite”, Insuwan teaches zeolite L adsorbs ammonia (page 346, left col. para. 3 and right col. para. 1; page 347, right col. para. 2; Figure 3; Table 2). Insuwan teaches zeolite L has ion exchange properties as the H form of zeolite L (H-LTL) was prepared by ion exchange of the K form of zeolite L (K-LTL) with ammonium nitrate resulting in ammonium-bound zeolite L (NH4-LTL) which was subsequently calcined to decompose NH4+ to NH3 (page 346, left col. para. 2). Insuwan teaches zeolite L adsorbs the dye AF and the lone pair of electrons of the amino group of AF interacts with zeolite L via hydrogen bonding (page 351, right col. para. 3; Scheme 1). Insuwan teaches it is possible that the acidic sites on zeolite L donate a proton to the amino group of AF to form -NH3+ which would be attracted to anionic sites of zeolite frameworks (page 351, right col. para. 3). Therefore, Insuwan teaches zeolite L adsorbs ammonia. Because zeolite L of Insuwan and zeolite A of Nayve are chemically very similar and only differ in geometrical properties as evidenced by Calzaferri (page 216, left col. last para.; Figure 2), and Nayve teaches 5 zeolites (natural and synthetic) that can adsorb similar amounts of ammonia (Table 1), one would have been motivated to combine the teachings of Nayve regarding an ammonia adsorbent that is a zeolite A with the teachings of Insuwan regarding an ammonia adsorbent that is zeolite L because both zeolites have similar chemical compositions and both can adsorb ammonia. Insuwan does not teach “wherein an amount of the L-type zeolite in the solution is between 0.025 g/mL and 0.1 g/mL”.
Kondo teaches an ammonia adsorbent that includes any substance that adsorbs ammonia including ion exchange resin and addition of the ammonia adsorbent to a culture solution of cells where the ammonia adsorbent can efficiently adsorb ammonia (page 2, lines 27 – 30). Kondo teaches the ammonia adsorbent may be any substance that adsorbs ammonia where the added ammonia adsorbent is 0.1 to 20% added to the culture of the organism (page 2, lines 31 – 34). As Kondo teaches a range of percentages of ammonia adsorbent added to a culture and Nayve teaches 250 mL of culture media, Kondo and Nayve teach an ammonia adsorbent in solution is between 0.025 g/mL and 0.1 g/mL when the percent of adsorbent is 10% (250 mL * 10% = 25 g ammonia adsorbent; 25 g/250 mL = 0.1 g/mL). Additionally, it would be obvious to adjust the concentration, since it is a result-effective variable dependent on amount of ammonia desired to be absorbed and the culture conditions.
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Nayve regarding a zeolite ammonia adsorbent and method of removing ammonia by contacting ammonia with the zeolite with the teachings of Insuwan regarding zeolite L adsorbs ammonia and has ion exchange properties with the teachings of Kondo regarding an ammonia adsorbent can be an ion exchange resin that removes ammonia by contacting the adsorbent with ammonia to arrive at the claimed ammonia removal apparatus comprising a culture vessel housing cells or microorganisms and a culture solution of the cells or the microorganisms; an adsorption module having an ammonia adsorbent; and a circulation path connecting the culture vessel and the adsorption module so as to allow the culture solution separated from the cells or the microorganisms to circulate between the culture vessel and the adsorption module to bring the culture solution in contact with the ammonia adsorbent, wherein the culture solution contains ammonia and glucose, wherein the ammonia adsorbent includes zeolite A and an L-type zeolite wherein an amount of the L-type zeolite in the culture solution is between 0.025 g/mL and 0.1 g/mL and wherein the amount of the L-type zeolite in the culture solution is an amount of the ammonia adsorbent relative to an amount of the culture solution adapted to be housed in the adsorption module packed with the ammonia adsorbent. One would have been motivated to combine the teachings of Nayve, Insuwan, and Kondo in an ammonia adsorbent to remove ammonia from cell culture media because Nayve teaches there is a pressing necessity to develop a system for the reduction, if not the removal of toxic metabolites such as ammonia from cell culture systems and adsorption is an attractive alternative to physically remove accumulated metabolites from culture broth. One would have a reasonable expectation of success in combining the teachings as Nayve teaches ammonia removal with zeolite maintained cell viability above 90% and ammonia was effectively maintained below the inhibitory level, Insuwan teaches zeolite L adsorbs ammonia and has ion exchange capacity and Kondo teaches the ammonia adsorbent may be an ion exchange resin that adsorbs ammonia.
13. Claim(s) 8 remains rejected under 35 U.S.C. 103 as being unpatentable over Nayve (Nayve FR et. al. Cytotechnology. 1991 Jun;6(2):121-30; previously cited), hereinafter Nayve in view of Insuwan (Insuwan, Wilaiporn, et. al. Journal of Porous Materials 21.3 (2014): 345-354; previously cited), hereinafter Insuwan as evidenced by Calzaferri (Calzaferri, Gion, et al. Comptes Rendus Chimie 9.2 (2006): 214-225; previously cited), hereinafter Calzaferri in view of Kondo (JP-03119970-A; previously cited), hereinafter Kondo. A machine translation of JP-03119970-A was previously provided. The translation was performed on October 21, 2024 of pages 1 – 4 of the original document.
Regarding “taking out a culture solution of cells or microorganisms from a culture vessel that houses the cells or microorganisms and the culture solution; and circulating the culture solution between the culture vessel and an adsorption module having an ammonia adsorbent to bring the culture solution into contact with the ammonia adsorbent to remove ammonia”, Nayve teaches in Figure 1 a circulation path and a peristaltic pump for circulation of cell-free culture broth into the packed zeolite for ammonia removal (page 123, left col.; page 124, left col. para. 1).
Regarding “wherein the culture solution contains ammonia and glucose”, Nayve teaches E-RDF culture broth containing ammonia (page 122, right col. para. 3; Figure 5 and 6).
Regarding “wherein the ammonia adsorbent comprises at least one substance selected from the group consisting of L-type zeolite”, Nayve teaches zeolite A-3 (Figure 1) but does not teach “L-type zeolite”.
Regarding “wherein an amount of the L-type zeolite in the culture solution is between 0.025 g/mL and 0.1 g/mL” and “wherein the amount of the L-type zeolite in the culture solution is an amount of the ammonia adsorbent relative to an amount of the culture solution adapted to be housed in the adsorption module packed with the ammonia adsorbent”, Nayve teaches 200 mL of packed zeolite A-3 beads for removal of ammonia from culture broth in Figure 1 with a working volume of 250 mL of culture (page 122, right col. last para.; Figure 1; page 123, left col. para. 2) but does not teach the recited concentration range.
Nayve does not teach “L-type zeolite” or “wherein an amount of the L-type zeolite in the culture solution is between 0.025 g/mL and 0.1 g/mL”. However, Nayve teaches 200 mL of packed zeolite A-3 beads for removal of ammonia from culture broth in Figure 1 with a working volume of 250 mL of culture (page 122, right col. last para.; Figure 1; page 123, left col. para. 2). Nayve teaches both natural and synthetic zeolites can adsorb ammonia similarly as shown in Table 1 (page 124, right col. para. 2). Nayve teaches there is a pressing necessity to develop a system for the reduction, if not the removal of toxic metabolites such as ammonia from animal cell culture systems (page 121, left col. and right col. para. 1). Nayve teaches adsorption is an attractive alternative to physically remove accumulated metabolites from culture broth (page 122, left col. para. 2). Nayve teaches mouse-mouse hybridoma TO-405 cells have been reported to be especially susceptible to ammonia inhibition in serum-free medium (page 122, left col. last para.). Nayve teaches ammonia removal with zeolite maintained cell viability above 90% and ammonia was effectively maintained below the inhibitory level (page 126, right col. para. 2). Nayve teaches packed zeolite A-3 beads can selectively and effectively remove ammonia from the broth of hybridoma cell cultures and could also mean high MAb production (page 129, left col. para. 2).
Regarding “L-type zeolite”, Insuwan teaches zeolite L adsorbs ammonia (page 346, left col. para. 3 and right col. para. 1; page 347, right col. para. 2; Figure 3; Table 2). Insuwan teaches zeolite L has ion exchange properties as the H form of zeolite L (H-LTL) was prepared by ion exchange of the K form of zeolite L (K-LTL) with ammonium nitrate resulting in ammonium-bound zeolite L (NH4-LTL) which was subsequently calcined to decompose NH4+ to NH3 (page 346, left col. para. 2). Insuwan teaches zeolite L adsorbs the dye AF and the lone pair of electrons of the amino group of AF interacts with zeolite L via hydrogen bonding (page 351, right col. para. 3; Scheme 1). Insuwan teaches it is possible that the acidic sites on zeolite L donate a proton to the amino group of AF to form -NH3+ which would be attracted to anionic sites of zeolite frameworks (page 351, right col. para. 3). Therefore, Insuwan teaches zeolite L adsorbs ammonia. Because zeolite L of Insuwan and zeolite A of Nayve are chemically very similar and only differ in geometrical properties as evidenced by Calzaferri (page 216, left col. last para.; Figure 2), and Nayve teaches 5 zeolites (natural and synthetic) that can adsorb similar amounts of ammonia (Table 1), one would have been motivated to combine the teachings of Nayve regarding an ammonia adsorbent that is a zeolite A with the teachings of Insuwan regarding an ammonia adsorbent that is zeolite L because both zeolites have similar chemical compositions and both can adsorb ammonia. Insuwan does not teach “wherein an amount of the L-type zeolite in the solution is between 0.025 g/mL and 0.1 g/mL”.
Kondo teaches an ammonia adsorbent that includes any substance that adsorbs ammonia including ion exchange resin and addition of the ammonia adsorbent to a culture solution of cells where the ammonia adsorbent can efficiently adsorb ammonia (page 2, lines 27 – 30). Kondo teaches the ammonia adsorbent may be any substance that adsorbs ammonia where the added ammonia adsorbent is 0.1 to 20% added to the culture of the organism (page 2, lines 31 – 34). As Kondo teaches a range of percentages of ammonia adsorbent added to a culture and Nayve teaches 250 mL of culture media, Kondo and Nayve teach an ammonia adsorbent in solution is between 0.025 g/mL and 0.1 g/mL when the percent of adsorbent is 10% (250 mL * 10% = 25 g ammonia adsorbent; 25 g/250 mL = 0.1 g/mL). Additionally, it would be obvious to adjust the concentration, since it is a result-effective variable dependent on amount of ammonia desired to be absorbed and the culture conditions.
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Nayve regarding a zeolite ammonia adsorbent and method of removing ammonia by contacting ammonia with the zeolite with the teachings of Insuwan regarding zeolite L adsorbs ammonia and has ion exchange properties with the teachings of Kondo regarding an ammonia adsorbent can be an ion exchange resin that removes ammonia by contacting the adsorbent with ammonia to arrive at the claimed method for removing ammonia comprising taking out a culture solution of cells or [[the]] microorganisms from a culture vessel that houses the cells or microorganisms and the culture solution; and circulating the culture solution between the culture vessel and an adsorption module having an ammonia adsorbent to bring the culture solution into contact with the ammonia adsorbent to remove ammonia, wherein the culture solution contains ammonia and glucose, wherein the ammonia adsorbent comprises zeolite A and an L-type zeolite, wherein an amount of the L-type zeolite in the culture solution is between 0.025 g/mL and 0.1 g/mL and wherein the amount of the L-type zeolite in the culture solution is an amount of the ammonia adsorbent relative to an amount of the culture solution adapted to be housed in the adsorption module packed with the ammonia adsorbent. One would have been motivated to combine the teachings of Nayve, Insuwan, and Kondo in an ammonia adsorbent to remove ammonia from cell culture media because Nayve teaches there is a pressing necessity to develop a system for the reduction, if not the removal of toxic metabolites such as ammonia from cell culture systems and adsorption is an attractive alternative to physically remove accumulated metabolites from culture broth. One would have a reasonable expectation of success in combining the teachings as Nayve teaches ammonia removal with zeolite maintained cell viability above 90% and ammonia was effectively maintained below the inhibitory level, Insuwan teaches zeolite L adsorbs ammonia and has ion exchange capacity and Kondo teaches the ammonia adsorbent may be an ion exchange resin that adsorbs ammonia.
Applicant’s Arguments/ Response to Arguments
14. Applicant Argues: On page 5 para. 2, Applicant asserts that Insuwan does not teach adsorbing ammonia in a culture solution by type-L zeolite or discuss the rate of glucose adsorption of type-L zeolite.
Response to Arguments: This is not found persuasive because Nayve teaches synthetic zeolite A-3 in contact with a solution containing ammonia and glucose (E-RDF medium) and cells to adsorb ammonia and Insuwan teaches zeolite L adsorbs ammonia in a solution of ammonia (page 346, left col. para. 3 and right col. para. 1; page 347, right col. para. 2; Figure 3; Table 2). Because Insuwan teaches zeolite L adsorbs ammonia in a solution of ammonia (page 346, left col. para. 3, previously cited), one of ordinary skill in the art would have a reasonable expectation that zeolite L would adsorb ammonia in a culture solution.
Applicant Argues: On page 5 para. 3, Applicant asserts that it could not have been possible to predict and would not have been obvious from Nayve in view of Insuwan whether type-L zeolite exhibits a higher rate of ammonia adsorption in a culture solution than other zeolites or selectively adsorbs ammonia more than glucose and skilled person would not have been motivated to combine Nayve with the type-L zeolite of Insuwan. On page 5, para. 7, Applicant asserts that the claimed subject matter provides an advantage that could not have been predicted from Nayve or Insuwan.
Response to Arguments: Solely to rebut Applicant’s arguments, these properties would have been obvious from Nayve in view of Insuwan as evidenced by Calzaferri because zeolite L of Insuwan and zeolite A of Nayve are chemically very similar and only differ in geometrical properties as evidenced by Calzaferri (page 216, left col. last para.; Figure 2, previously cited). To elaborate in rebuttal of Applicant’s arguments, Figure 2 of Calzaferri shows the frameworks of LTA and LTL and one of ordinary skill in the art would predict that because LTA and LTL are chemically similar and LTL has a channel system, the rate of ammonia adsorption would be higher for LTL than LTA due to its cages versus LTL’s channel system. It is known in the art that zeolites adsorb ammonia as this is a way to characterize the acid sites of zeolites as taught by Insuwan (page 347, right col. para. 2; previously cited). Therefore, one of ordinary skill in the art would predict selective adsorption of ammonia more than glucose by zeolites including LTL zeolites.
Applicant Argues: On page 5, para. 4 – 5, Applicant asserts that it should be predicted that the adsorption performance of type-L zeolite is lower than that of Y-type zeolite or mordenite.
Response to Arguments: The maintained rejection cites teachings of zeolite A-3 and not Y-type zeolite.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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.
/ZANNA MARIA BEHARRY/Examiner, Art Unit 1632
Prosecution Insights