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 .
Applicant's amendments to the claims and arguments filed on 10-07-2025 have been received and entered. Claims 1, 7, have been amended. Claims 2, 6, 8-9, 15-21, 28-33 have been canceled. Claims 1, 3-5, 7, 10-14, 22-27 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of elects Group I (claims 1-5, 7-14) in the reply filed on 04-22-2024 is acknowledged.
Claims 22-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on.
Claims 1, 3-5, 7, 10-14 are under consideration.
Priority
This application is a 371 of PCT/JP2019/043031 filed on11/01/2019 that claim priority from US provisional application 62/754,793 filed on 11/02/2018.
Maintained in modified form- Claim Rejections - 35 USC § 103 - necessitated by amendments
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.
Claims 1, 3-5, 7, 10, 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Konno et al (Pub. No.: US 2013/0267684 A1, Pub. Date: Oct. 10, 2013) in view of Kaschak et al (mAbs 3:6, 577-583; November/December 2011, DOI: 10.4161/mabs.3.6.17959) and Teixeira et al (Stem Cell Research & Therapy (2015) 6:133, DOI 10.1186/s13287-015-0124-z) as evidenced by Rafiq et al (Biotechnol. J. 2013, 8, 459–471; DOI 10.1002/biot.201200197).
Claims interpretation:
According to the specification of the claimed invention, the method for culturing cells in the invention is a method suitable for the cells used, such as batch culture, repeated batch culture, rolling seed culture, fed-batch culture and perfusion culture ([0081], Page 18). Therefore, the method for preparing a liquid medium can be used in perfusion culturing methods.
The specification of the claimed invention teaches that the gas containing oxygen is not particularly limited as long as the gas contains oxygen, and examples include pure oxygen, a mixture of oxygen and another gas, air and the like. When the gas containing oxygen is a mixture of oxygen and another gas, the other gas is nitrogen, argon, helium, carbon dioxide or the like. One or more gases thereof and oxygen are prepared at any mixing ratio and supplied ([0049], page 11-12). During the preparation of the liquid medium of the invention, the concentration or the amount of the supplied oxygen is not particularly limited as long as the medium components such as copper dissolve sufficiently and do not precipitate with the amount, and the concentration or the amount is preferably adjusted in such a manner that the solvent or the prepared liquid medium contains oxygen in an amount of 20% or more, The amount is maintained at more preferably 20% or more, further preferably 40% or more of the saturated dissolved oxygen ([0050], page 11-12). Thus, air and the like with oxygen for the medium components such as copper to dissolve sufficiently are interpreted to be able to use in the invention.
The specification of the claimed invention teaches that air was sent to one of the containers from the bottom surface, and the dissolved oxygen concentration was saturated. A mixture gas of nitrogen and oxygen was sent to the remaining three containers, and the dissolved oxygen concentrations were controlled to 40%, 20% or 0% ([0127], page 29). Thus, sending air into medium is interpreted as a mean to control dissolved oxygen concentrations.
The specification of the claimed invention teaches that “By stirring, the powder medium and the oxygen can be dissolved in the solvent. The stirring is conducted by rotating a stirring blade, for example, at a speed of 1 to 200 rpm. Moreover, also through spontaneous mixing by sending a gas containing oxygen from the bottom surface of the solvent or the prepared liquid medium, the powder medium and the oxygen can be dissolved.” ([0053], page 12). Thus, the powder medium can be dissolved in the solvent by mixing.
Regarding to claim 1, the preamble, Konno et al teaches method for preparing aqueous solution containing culture medium and chelating agent (Title). The culture medium is a powdered culture medium, a liquid culture medium, or a slurry culture medium ([0020], page 2). Also, Preparation of the aqueous solution: 22.6 g of improved powder culture medium EXCELL 302 containing amino acids, metal salts, vitamins and the like was dissolved in PBS, followed by stirring for about 30 minutes ([0211], page 13). In addition, a dissolved oxygen concentration control can be used ([0119], page 7).
Regarding to claim 1, the claimed “wherein the powder medium comprises copper or a derivative thereof”: Konno et al teach the metal may include copper ([0074], page 4).
Konno et al does not specifically teach an operation of sending the gas containing oxygen to an upper surface of the solvent, or operation of sparging the gas containing oxygen into the solvent. Kaschak et al cure the deficiency.
Regarding to claim 1, the claimed “at least one operation selected from the following (i) and (ii)”, Kaschak et al teach chemically-defined medium in 2 L bioreactors equipped with calibrated dissolved oxygen, pH and temperature probes. Temperature control was achieved via a heating blanket. Dissolved oxygen was controlled on-line through sparging with air or oxygen (Page 580, right column, last paragraph).
Regarding to claim 1, the claimed “ the powder medium is being dissolved in the solvent” and “powder medium is being dissolved in the solvent, thus bringing the gas into contact with the solvent during the dissolving step”: Konno et al teach “improved powder culture medium EX-CELL 302 (manufactured by SAFC Bioscience) …… dissolved in PBS were added, followed by stirring for about 30 minutes.” ([0176], page 11). Additionally, Kaschak et al teach “chemically-defined medium in 2 L bioreactors equipped with calibrated dissolved oxygen, pH and temperature probes ……Dissolved oxygen was controlled on-line through sparging with air or oxygen” (Page 580, right column, last paragraph). Thus, the arts teach the use of mixing/ sparging with air or oxygen of powder medium/medium components as evidence by applicant disclosure: “By stirring, the powder medium and the oxygen can be dissolved in the solvent ….through spontaneous mixing by sending a gas containing oxygen from the bottom surface of the solvent or the prepared liquid medium, the powder medium and the oxygen can be dissolved.” ([0053], page 12).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Konno et al by controlling dissolved oxygen through sparging with air or oxygen as taught by Kaschak et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Kaschak et al provide explicit advantage of development of a new chemically defined medium (CDM) platform cell culture process and supplementing copper in the production medium above the original levels in the historical medium formulation helped maintain cell viability and improve mAb titers (Page 577, right column, 2nd para). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Kaschak et al were successful in increasing cell density and improving titer (Page 580, right column 2nd para) with detailed instructions and working example.
Regarding to claim 1, the claimed “further comprising a step of membrane filtration after the step of dissolving the powder medium in the solvent in the presence of a gas containing oxygen, Konno et al provide a method for performing membrane filtration of the aqueous solution which is prepared by the preparation method of the aqueous solution, a method for improving membrane filter ability of the aqueous solution (Abstract). Konno et al teaches that, in the preparation of the aqueous solution containing the powder culture medium, the filterability-improving effects of the chelating agents were examined by using a plurality of filtration membranes ([0209], page 13, example 4). The filter was connected to the tank, and 100 kPa of pressure was applied by the compressed air ([0212], page 13).
Although Konno et al teach dissolved oxygen concentration control ([0119], page 7), Konno et al do not specify solvent contains an amount of dissolved oxygen of 20% or more of a saturated dissolved oxygen during the step of dissolving the powder medium. Teixeira et al cure the deficiency.
Regarding to claim 1, the claimed “wherein the solvent contains an amount of dissolved oxygen of 20% or more of a saturated dissolved oxygen during the step of dissolving the powder medium,” Teixeira et al teach preparation of 500 mL suspension bioreactors prior to inoculating hWJ-MSCs in the DASGIP bioreactors: The bioreactors were maintained at: (1) 37 °C using a heating jacket; (2) 100 % dissolved oxygen (corresponding to oxygen saturation of the medium at 37 °C exposed to 21 % O2 in the headspace) for normoxic conditions; (3) 21 % dissolved oxygen (corresponding to oxygen saturation of the medium at 37 °C exposed to 5 % O2 in the headspace) for hypoxic conditions; (4) pH of 7.4, controlled by a gas mixture connected to oxygen, nitrogen, carbon dioxide and air tanks that was introduced into the headspace; and (5) agitation of 52 rpm using a magnetic stir plate under the bioreactors (Page 3, left column, 1st para.).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Konno et al and Kaschak et al by maintaining 100 % dissolved oxygen (21 % O2 in the headspace for normoxic conditions) or 21 % dissolved oxygen (5 % O2 in the headspace for hypoxic conditions) as taught by Teixeira et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Teixeira et al demonstrated that the secretomes of hWJ-MSCs collected from normoxic and hypoxic conditions were able to induce neuronal differentiation of hNPCs into neurons in different stages of maturation. These outcomes were associated with the presence of important neuroregulatory molecules within the constitution of the secretomes such as GDN, Cys C, UCHL1, clusterin, Prx1, 14-3-3, thymosin-beta and EF- 2. These are important molecules involved in the promotion of neuroprotection, inhibition of apoptosis, angiogenesis and neuronal cell survival and differentiation (Page 11, left column, 2nd para). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Teixeira et al were successful in using normoxic and hypoxic conditions for culturing and differentiating MSCs cells with working examples and data.
As evidenced by Rafiq et al, the levels of oxygen usually described by the term “normoxia” (20–21% v/v oxygen in the headspace) is equivalent to 100% dissolved oxygen (dO2) in the culture medium when saturated with respect to air; whilst the term “hypoxia” (2–5% v/v oxygen) is equivalent to 10–25% dO2 (Page 460, left column, last para). Thus, in a cell culture medium, even deliberately exposing medium in hypoxia condition (0.5% and 10% in the headspace), the dissolved oxygen in the medium can reach up to 25% dO2 .
PNG
media_image1.png
223
899
media_image1.png
Greyscale
Regarding to claims 3-4, Kaschak et al teach target copper concentrations of 400, 550, 750 and 1,000 nM were achieved via direct addition of 1 mM copper sulfate stock solution to media from a single basal media preparation (Page 580, right column, last paragraph).
Regarding to claim 5, Konno et al teach examples of the amino acids may include, but is not particularly limited to, for example, L-alanyl-L-cysteine or the like are exemplified ([0071], page 4).
Regarding to claim 7, Konno et al teach 22.6 g of improved powder culture medium EXCELL 302 dissolved in PBS followed by stirring for about 30 minutes ([0211], page 13).
Regarding to claim 10, Konno et al teach the filterability-improving effects of the chelating agents were examined by using a plurality of filtration membranes. As a result, it was revealed that Vmax (maximum processing amount per unit membrane area) value can be improved by a polyvinylidene fluoride (hereinafter, referred to as PVDF) membrane with a pore size of 0.22 µm ([0209], page 13).
Regarding to claim 13, Teixeira et al teach preparation of 500 mL suspension bioreactors prior to inoculating hWJ-MSCs in the DASGIP bioreactors: The bioreactors were maintained at: (1) 37 °C using a heating jacket; (2) 100 % dissolved oxygen (corresponding to oxygen saturation of the medium at 37 °C exposed to 21 % O2 in the headspace) for normoxic conditions; (3) 21 % dissolved oxygen (corresponding to oxygen saturation of the medium at 37 °C exposed to 5 % O2 in the headspace) for hypoxic conditions (Page 3, left column, 1st para.).
Regarding to claim 14, Konno et al teach that the culture method may be carried out in any culture volume, for example, a large culture volume of from 1 to 20000 L for commercial production typically using a culture vessel or the like such as jars ([0121], page 7).
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Konno et al (Pub. No.: US 2013/0267684 A1, Pub. Date: Oct. 10, 2013) in view of Kaschak et al (mAbs 3:6, 577-583; November/December 2011, DOI: 10.4161/mabs.3.6.17959) and Teixeira et al (Stem Cell Research & Therapy (2015) 6:133, DOI 10.1186/s13287-015-0124-z) as evidenced by Rafiq et al (Biotechnol. J. 2013, 8, 459–471; DOI 10.1002/biot.201200197) as applied to claims 1, 3-5, 7, 10, 13-14 above, further in view of Villiger-Oberbek et al (Pub. No.: US 2016/0017280 A1, Pub. Date: Jan. 21, 2016).
The above combined refences are as described above. The above references do not teach measuring dissolved oxygen. Villiger-Oberbek et al cure the deficiency.
Regarding to claims 11-12, Villiger-Oberbek et al teaches culture media: the first and/or second liquid culture medium can be a chemically-defined liquid culture medium ([0110]-[0111], page 12) and the use of copper sulfate ([0026], page 3). Also, dissolved O2 levels in a liquid culture medium can be detected using a variety of different methods. For example, dissolved O2 can be measured using a dissolved O2 electrode or probe ([0155], page 19). The term "dissolved O2 concentration" or "dissolved oxygen concentration" means the amount of oxygen gas dissolved in a liquid culture medium (e.g., any of the liquid culture media described herein or known in the art) ([0039], page 4).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of the above combined references by measuring and detecting dissolved oxygen concentration such as using a dissolved O2 electrode or probe as taught by Villiger-Oberbek et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Villiger-Oberbek et al provide explicit advantage of using a variety of cell culture parameters that can be adjusted to achieve a specific dissolved O2 concentration and a specific fluid sheer force ([0154], page 19). Villiger-Oberbek et al also stated that culturing a mammalian cell in a multi-well plate in the specific manner described herein results in a substantially improved viable cell density and recombinant protein production, and provides an accurate model of culture performance in large-scale perfusion, production bioreactors ([0004], page 1). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Villiger-Oberbek et al were successful in generation of cultures that maintained a percentage cell viability of above 85% (FIG. 7) ([0190], page 23).
Response to Arguments
Applicant's arguments filed 10-07-2025 have been fully considered but they are not persuasive.
1. Applicants argue that it is asserted that Teixeira fails to provide any relevant teachings on this point. At most, Teixeira appears to teach maintaining a bioreactor under the conditions recited by the Examiner, i.e. (1) 37°C using a heating jacket; (2) 100% dissolved oxygen (corresponding to oxygen saturation of the medium at 37°C exposed to 21% 02 in the headspace) for normoxic conditions; (3) 21% dissolved oxygen (corresponding to oxygen saturation of the medium at 37°C exposed to 5% 02 in the headspace) for hypoxic conditions; (4) pH of 7.4, controlled by a gas mixture connected to oxygen, nitrogen, carbon dioxide and air tanks that was introduced into the headspace; and (5) agitation of 52 rpm using a magnetic stir plate under the bioreactors).
There is no teaching or even a suggestion that the culture media in the bioreactor "contains an amount of dissolved oxygen of 20% or more of a saturated dissolved oxygen during the step of dissolving the powder medium" as recited in claim 1 Instead, the only reference to the culture media in Teixeira is a statement that PPRF-msc6 media is used in the bioreactor (see page 3, middle of left column and bottom of left column). Teixeira fails to providing any information on how the PPRF-msc6 media is prepared. As the manner in which the media is prepared is the fundamental basis of the claimed method, the absence of any teaching whatsoever with respect to the manner in which the media of Teixeira was prepared is fatal flaw in the publication. (Remarks, page 6-7)
Response to arguments:
As Applicant admitted, Teixeira et al teach maintaining a bioreactor under 100% dissolved oxygen (corresponding to oxygen saturation of the medium at 37°C exposed to 21% O2 in the headspace) for normoxic conditions, and 21% dissolved oxygen (corresponding to oxygen saturation of the medium at 37°C exposed to 5% O2 in the headspace) for hypoxic conditions. Thus, even deliberately using hypoxic conditions, it is evidenced by the prior arts that the medium/solvent contains an amount of dissolved oxygen of 21% or more.
There is no evidence provided by applicant that the culture media in the bioreactor do not “contains an amount of dissolved oxygen of 20% or more of a saturated dissolved oxygen during the step of dissolving the powder medium”. It is because as evidenced by the cited reference Teixeira et al teach hypoxic conditions with 21% dissolved oxygen. Thus, even under hypoxic conditions, there is 21% dissolved oxygen in the medium let alone in normoxic conditions that have 100% dissolved oxygen in the medium. Since none of the cited Prior art even tried hypoxic conditions, they prepared medium in normoxic conditions that have 100% dissolved oxygen.
As evidenced by Rafiq et al, the levels of oxygen usually described by the term “normoxia” (20–21% v/v oxygen in the headspace) is equivalent to 100% dissolved oxygen (dO2) in the culture medium when saturated with respect to air; whilst the term “hypoxia” (2–5% v/v oxygen) is equivalent to 10–25% dO2 (Page 460, left column, last para). Thus, in a cell culture medium, even deliberately exposing medium in hypoxia condition (0.5% and 10% in the headspace), the dissolved oxygen in the medium can reach up to 25% dO2 .
PNG
media_image1.png
223
899
media_image1.png
Greyscale
Additionally, Konno et al teach preparation of the aqueous solution: 22.6 g of improved powder culture medium EXCELL 302 was dissolved in PBS, followed by stirring for about 30 minutes ([0211], page 13). As evidence by applicant disclosure: “By stirring, the powder medium and the oxygen can be dissolved in the solvent.” ([0053], page 12). Since Konno et al do not teach preparation of the aqueous solution in hypoxia condition, the dissolved oxygen should be under normoxic conditions that have 100% dissolved oxygen, as evidenced by Rafiq et al.
According to MPEP 716.01(c) (II), arguments by applicant cannot take the place of evidence: Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
2. Applicants argue that it must also be recognized that Teixeira does not disclose filtration of medium and it is silent about copper concentration. Thus, Teixeira does not suggest the problem found in the present invention, let alone provide any motivation to set the amount of dissolved oxygen as 20% or more during the step of dissolving the powder medium into the solvent for solving the problem. Teixeira merely discloses controlling oxygen concentration in medium during cell culture. Similarly, none of Konno, Kaschak and Rafiq discloses or suggests the problem to be solved by the present invention or control of the dissolved oxygen concentration in the solvent during the step of dissolving the powder medium. Therefore, the claimed method could not have been easily conceived by a skilled person reading the combination of cited art.
Response to arguments:
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Konno et al teach method for preparing aqueous solution containing culture medium and chelating agent (Title), and the culture medium is a powdered culture medium ([0020], page 2). Konno et al teach preparation of the aqueous solution: 22.6 g of improved powder culture medium EXCELL 302 was dissolved in PBS, followed by stirring for about 30 minutes ([0211], page 13), and dissolved oxygen concentration control can be used ([0119], page 7), and the metal in medium may include copper ([0074], page 4). Additionally, Kaschak et al teach chemically-defined medium in 2 L bioreactors equipped with calibrated dissolved oxygen, pH and temperature probes. Temperature control was achieved via a heating blanket. Dissolved oxygen was controlled on-line through sparging with air or oxygen (Page 580, right column, last paragraph). Thus, a person of ordinary skill in the art would be able to use sparging with air or oxygen as taught by Kaschak et al as an approach to preform stirring as taught by Konno et al. One of ordinary skill in the art would have been motivated to combine the prior arts because Kaschak et al provide explicit advantage of development of a new chemically defined medium (CDM) platform cell culture process and supplementing copper in the production medium above the original levels in the historical medium formulation helped maintain cell viability and improve mAb titers (Page 577, right column, 2nd para).
Additionally, Konno et al provide a method for performing membrane filtration of the aqueous solution which is prepared by the preparation method of the aqueous solution, a method for improving membrane filter ability of the aqueous solution (Abstract). Konno et al teaches that, in the preparation of the aqueous solution containing the powder culture medium, the filterability-improving effects of the chelating agents were examined by using a plurality of filtration membranes ([0209], page 13, example 4). The filter was connected to the tank, and 100 kPa of pressure was applied by the compressed air ([0212], page 13).
3. Applicants argue that it is important to recognize that the recited value of dissolved oxygen present during the step of dissolving the powder medium has an advantageous effect. As shown in Example I of the present specification, the inventors realized the problem, for the first time, that when the dissolved oxygen concentration is low during the step of dissolving the powder medium into the solvent, copper is unacceptably removed during the later step of media filtration, and the copper concentration decreases. Example 2 and Fig. 2 demonstrate that the decrease in the copper concentration after media filtration is prevented when the medium is prepared by dissolving the powder medium into the solvent containing an amount of dissolved oxygen of 20% or more of a saturated dissolved oxygen.
Furthermore, Example 3 and Fig. 3 demonstrate that when the cells producing antibodies are cultured in the medium prepared by the above conditions, the decrease in the percentage of basic variants of the produced antibody can be prevented. The combination of cited art fails to disclose or suggest these advantageous effects (Remarks, pages 7-8).
Response to arguments:
It is noted that Kaschak et al teach (i) “a new chemically defined medium (CDM) platform cell culture process and supplementing copper in the production medium above the original levels in the historical medium formulation helped maintain cell viability and improve mAb titers. Here, we present a case study demonstrating the impact of copper concentration in the production media on the charge profiles of an IgG1” (Page 577, right column, 2nd para); (ii) “Copper titration study: …… Dissolved oxygen was controlled on-line through sparging with air or oxygen, and pH was controlled through additions of CO2 or 1M Na2CO3.” (Page 580, right column, last para.). Thus, taken together (i) and (ii), It is indicating that the copper concentrations under controlled dissolved oxygen were recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform the controlling copper concentrations under controlled dissolved oxygen to obtain optimal copper concentrations for maintaining cell viability and improving mAb titers as taught by Kaschak et al out of the course of routine optimization.
Given that preparing medium under atmospheric condition (normoxic conditions with 20% of oxygen in the air) not under hypoxic conditions is routinely performed in the art. Applicant’s discovery of effect of oxygen on copper concentration is inherent for mixing powder medium under normal atmospheric or controlled oxygen level (dissolved oxygen of 20%) as taught by prior arts. According to MPEP 2112 (II), inherent feature need not be recognized at the relevant time, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
In response to applicant's argument that “the recited value of dissolved oxygen present during the step of dissolving the powder medium has an advantageous effect.”, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
3. Applicants argue that
The Examiner discounts some of the arguments with respect to the experimental data provided in the specification (see "Response to Arguments" on pages 12-13 of the Action). To buttress Applicant's position, reference can be made to the priority application (US 62/754,793), especially page 19, a copy of which is attached. It is asserted that none of the cited art, alone or in combination, discloses or suggests that an amount of dissolved oxygen is adjusted to 20% or more of a saturated dissolved oxygen when the powder medium is dissolved into the solvent
The Examiner suggests that in the Examples of the present specification, the copper
concentration was decreased as a result of deliberately sending nitrogen to remove oxygen, and
that the copper concentration would not be affected under atmospheric air condition.
However, as shown on page 19 of the priority application, the dissolved oxygen concentration decreases when a powdered medium is dissolved in a solvent, and this decrease is particularly significant at manufacturing scale. Furthermore, it was first discovered by the present inventors that when the dissolved oxygen concentration decreases during medium preparation, the copper concentration after filtration decreases. Thus, a decrease in dissolved oxygen concentration can occur even under atmospheric air depending on the conditions. Contrary to the Examiner's assertion, the Example of the present specification is not a state artificially created to be one that would not ordinarily occur.
In the Example of the present specification, nitrogen was sparged to create a low dissolved oxygen condition and thereby reproduce the problem of decreased copper concentration. Then, it was shown for the first time that the problem could be solved by increasing the dissolved oxygen concentration by sending a gas containing oxygen (Remarks, page 8).
Response to arguments:
The claims do not specify any conditions to decrease oxygen concentration under manufacturing scale or laboratory scale, and do not specify what oxygen concentration would significantly decrease copper concentration. On page 18 of the power point slides submitted as specification in the priority application US 62/754,793 compared effect of dissolved oxygen of 100% and 0% on copper concentration (page 18), and on page 19, the priority application discloses decrease of oxygen concentration to 0% under manufacturing scale; however, the priority application and the instant disclosure do not provide any guidance for what is considered to be manufacturing scale (how big? or arbitrary scale) to cause dissolved oxygen of 0%.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a decrease in dissolved oxygen concentration can occur even under atmospheric air depending on the conditions) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Nevertheless, as explained above, the copper concentrations under controlled dissolved oxygen were recognized in the prior art to be a result-effective variable. One of ordinary skill in the art would be motivated to control copper concentrations out of the course of routine optimization. Further, the Examiner has previously explained that under the conditions of the cited art, the dissolved oxygen concentration would not have fallen below 20%: none of the cited prior art teach the use dissolved oxygen of 0% for preparing medium, and with the cited prior arts, one of ordinary skill in the art would not look for and perform medium preparation under dissolved oxygen of 0%. Even Teixeira et al teach 21% dissolved oxygen (corresponding to oxygen saturation of the medium at 37°C exposed to 5% O2 in the headspace) for hypoxic conditions. Thus, applicant arguments regarding to advantageous/unexpected effects are not persuasive.
4. Applicants argue that it is again submitted that the combination of Konno, Kaschak, Teixeira and Rafiq fail to teach or suggest a method for preparing a liquid medium where "the solvent contains an amount of dissolved oxygen of 20% or more of a saturated dissolved oxygen during the step of dissolving the powder medium." Villiger-Oberbek fails to cure the defects of Konno, Kaschak, Teixeira and Rafiq. Therefore, claim 1 must be recognized as being non-obvious in view of the combination of Konno, Kaschak, Teixeira, Rafiq and Villiger-Oberbek. (Remarks, page 9)
Response to arguments:
Arguments drawn to Konno, Kaschak, Teixeira and Rafiq have been addressed above and will not be addressed herein. Moreover, Villiger-Oberbek reference was not cited to teach any limitation found in independent claim 1.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHOA NHAT TRAN whose telephone number is (571)270-0201. The examiner can normally be reached M-F (9-5).
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.
/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632