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 .
Priority
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. KR10-2018-0033828, filed on Sept. 23, 2020.
Claim Status
In the reply filed on Sept. 5, 2025, Applicant has amended claim 1, and canceled claims 3, 9-14, 16, and 18-24.
Currently, claims 1-2, 4-8, 15, and 17 are under examination.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The rejection of claim 1 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn due to Applicants amendment of step (d) to recite “the population of NK cells of step (c)”.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/05/2025 was filed after the mailing date of the Non-final Action on 5/5/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: missing units or reference word. The claim recites “wherein the accumulated population doubling level of the NK cells in the bioreactor reaches at least 3.8, the killing activity (10:1) of the NK cells in the bioreactor reaches at least 93, and the killing activity (3: 1) of the NK cells in the bioreactor reaches at least 73 within 8-10 days” and does not recite units. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 4-8, 15 and 17 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.
This rejection is a new rejection necessitated by amendments to the claims.
Claim 1 recites the limitation of “the target NK cell concentration is about 0.7X106 cells/mL” in line 14. However, there is no previous recitation of a “target NK cell concentration.” There is insufficient antecedent basis for the limitation of “the target NK cell concentration” in the claim. It is unclear what NK cell concentration that is being referred to in the claim. For compact prosecution this step will be interpreted as any NK cell concentration having about 0.7X106 cells/mL.
Claim 1 recites the claim limitation of “the killing activity (10:1) of the NK cells in the bioreactor”, and “the killing activity (3:1) of the NK cells in the bioreactor.” It is unclear what the ratio of 10:1 or 3:1 of the killing activity of NK cells is being referred to in the claim. In the specification that the appears that the ratio of 10:1 or 3:1 is a titer (para. 166 and Table 7), but it is unclear what the titer ratio represents 10:1 or 3:1 (e.g. population of NK cells to donor or NK cells to feeder etc.). Further, it is unclear what the titer means regarding the killing activity of the NK cells. The MPEP recites that “Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. The reference characters, however, should be enclosed within parentheses so as to avoid confusion with other numbers or characters which may appear in the claims. Generally, the presence or absence of such reference characters does not affect the scope of a claim”. MPEP608.01(m). As such, the claim does not clearly define what the ratios of 10:1 or 3:1 represents and what is being referred to in the claim. Furthermore, there are numerous possibility of what the ratio of 10:1 or 3:1 means. Therefore, it is unclear of the ratios represent and what is being referring to in the claim.
Regarding claim 1, the phrase “the killing activity (10:1)” and “the killing activity (3:1)” renders the claim indefinite because it is unclear whether the limitations (i.e. ratios) following the phrase (i.e. killing activity) are explicit or required as part of the claimed invention. Furthermore, it is unclear how the killing activity is related to the ratio of 10:1 or the ratio of 3:1 since killing activity is not known as a ratio. Thus, the parathesis renders the claim indefinite because it is unclear if the claims include elements that are not actually disclosed, thereby rendering the scope of the claims unascertainable. See MPEP § 2173.05(d).
Claim 1 recites “the killing activity (10:1) of the NK cells in the bioreactor reaches at least 93, and the killing activity (3: 1) of the NK cells in the bioreactor reaches at least 73 within 8-10 days.” It is unclear what the value of 73 and 93 refer to in the claim. For example, is the value related to the bioreactor or to the killing activity of NK cells. As such there are numerous possibility that the values may be referring too. In the Specification, Fig. 7 recites “FIG. 7 shows prediction profilers of accumulated population doubling level, cell concentration at the end of culturing, titer (10:1) and titer (3:1) depending on the temperature of an agitated bioreactor, pH, inoculated cell concentration and target cell concentration”. It is noted that in Fig. 7, it appears that the killing activity titer of 10:1 has the lowest value of 93, and the titer of 3:1 has the lowest value of 73 (see fig. 7, y-axis values). However, it is unclear what the values of 93 and 73 are being referred to in the claim (e.g. fold, cell population, percentage etc.). Further, the specification and the drawings do not disclose the y-axis of figure 7. Therefore, it is unclear of the values represent and what is being referring to in the claim.
In the interest of compact prosecution, the claimed titer ratios and levels will be interpreted as referring to the cell population levels recited in the claims. (See support Specification para. 166, “The culture conditions for maintaining all of the accumulated population doubling level, titer (10:1) and titer (3:1) the highest are: inoculated cell density 1.0×106 cells/mL, target cell concentration 0.7×106 cells/mL, temperature 36° C. and pH 7”).
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.
Claims 1-2, 4-8, 15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Min et al. (WO2016/085248A1, 2016, on IDS 08/11/2021, prior art of record) in view of Min et al., (WO2013/094988A1, published 2013, cited IDS 08/11/2021; hereinafter as “Min 2013”, prior art of record), Eibl et al., (Disposable bioreactors: 55-87; published 2009, prior art of record), Alici (US2012/0258085A1; published 2012, prior art of record), and Somerville, et al. (Journal of translational medicine 10: 1-11; published 2012, prior art of record).
This rejection is a new rejection necessitated by amendments to the claims. However, since it is substantially similar to a rejection set forth in the non-final Official action mailed on May 5, 2025, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 1, 15, and 17, Min discloses a method for producing Natural Killer (NK) cells (see e.g. abstract, claim 1, paras. 11 and 88-95, figs. 1-5; Examples 1-2). Min discloses step (a) a method wherein NK cells (mononuclear cells) are stimulated with feeder cells and stationary-cultured (see e.g. para. 88). Min discloses step (b), that following this, the stationary-cultured cells were cultured in suspension culture and restimulated with feeder cells (see e.g. para. 89 and 94). Min discloses step (c), that for re-stimulation, NK cells and feeder cells can be co-cultured in suspension culture (see e.g. para. 95). Min discloses that culturing is carried out for 5-60 days and that the re-stimulation is performed at intervals of 5-12 days (see e.g. claims 9 and 14), which reads on the claimed 8-10 days of culturing NK cells.
While Min does not explicitly state the specific number of doublings for when cells are restimulated, it should be noted that the claims do not require a specific number of cells, but only require a number of doublings. Min teaches that the addition of feeder cells leads to fold increases ranging from 21-fold to as high as 2752-fold (see e.g. para. 90-90, 96-97, and 103), and that previous method result in 3 to 10-fold increase in NK cells (see e.g. para. 6). Min also teaches that once frozen thawed mononuclear cells can be used as starting cells (see e.g. para. 74). Therefore, the fold-increases, as taught by Min, overlap with the doublings of 3-5 times (i.e. at least 3.8) as in claim 1.
Additionally, providing context for a workable example, the specification states that in one example, cells were counted and diluted to a concentration of 2x105 to 5x105 before restimulation (see e.g. para. 97, page 37, lines 20-23). In comparison, Min teaches that for restimulation, cells are diluted to a density of 2-5 x 102, and recounted and diluted at intervals of 2-3 days in suspension culture at the same density for up to 21 days (see e.g. para. 94) and that the re-stimulation is performed at intervals of 5-12 days (see e.g. claims 9 and 14).
Therefore, it appears that if Min does not teach a timing of restimulation at a doubling of 3-5 times, the method of Min is at least capable of performing the restimulation step at this timing.
Moreover, a person of ordinary skill in the arts could have arrived at a timing of re-stimulating the cells when the accumulated population level of mononuclear cells reaches 3-5 by routine optimization, and the disclosure does not point to a criticality in this regard (see MPEP 2144.05(II)(A)). In the instant case, because, as above, Min teaches that the addition of feeder cells leads to fold increases ranging from 21-fold to as high as 2752-fold (see e.g. para. 90-90, 96-97, and 103), which overlaps with doublings of 3-5 times, a person of ordinary skill in the art could have arrived at this timing by routine optimization with predictable results and a reasonable expectation of success.
Min silent regarding the bioreactor (i.e. the bioreactor’s pH, temperature, and agitation power), and inoculating a bioreactor with the cell culture comprising the concentration of NK cells that were obtained by stationary culture and then suspension culture sequentially.
However, Min cites the prior art of Min 2013 (WO2013094988A1)(see page 3), which teaches that bioreactors (i.e. reactors, e.g. Wave bioreactor) are commonly used for suspension cultures (see e.g. pages 7-8). Further, the prior art of Eibl discloses that bioreactors (e.g. Wave bioreactor) have optimum mass and energy transfer within the mechanically driven inflated culture bag, and the essential parameters such as rocking rate, rocking angle, vibration frequency, temperature and aeration rate are adjustable (see e.g. abstract and page 58).
Regarding claims 1, 15, and 17, Eibl discloses bioreactors (e.g. Wave bioreactors) for suspension culturing at an agitation speed of 30-300 rpm (see e.g. page 63, table 2).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Min to incorporate the suspension culturing as taught by Min 2013 and Eibl at the agitation speed of 30-300 rpm (or 60-160 rpm as in claim 17) as taught by Eibl because Eibl discloses that bioreactors (e.g. Wave bioreactor) are common devices in modern biotechnological processes that enable middle to high cell density and adequate productivity in laboratory and pilot scale (see e.g. abstract). Additionally, Min 2013 discloses examples of the reactor for suspension culture include, but are not limited to, a wave bioreactor (GE Healthcare), and a disposable shaker flask (Erlenmeyer) and so on (see e.g. pages 7-8). Therefore, a person of ordinary skill in the art would have incorporated the agitation speed of 30-300 rpm in the suspension culture, which would have led to predictable results with a reasonable expectation of success because both Min, Min 2013, and Eibl disclose that bioreactors are known to be used with suspension culturing. Furthermore, an artisan of ordinary skill in the art of (i.e. suspension-cultured cells) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 1(d), 15, and 17, Min discloses the cell density reaches 5-10x105 cells/mL (i.e. 500,000-1million) (see e.g. para. 89, 95, Example 2).
Min is silent regarding the concentration of NK cells in the bioreactor at the time of the inoculation and with the cell culture comprising the NK cells that were obtained by stationary culture and then suspension culture sequentially, as discussed above.
However, the prior art of Alici teaches expansion of natural killer cells in a closed automated culture system, for example using a bioreactor (see e.g. para. 1, abstract, and claim 1). Alici discloses inoculating NK cells (i.e. isolated cells from mononuclear cells) to a bioreactor for expansion(see e.g. claims 26, 44; para.23-32, 56-57, 73, and Example 1, fig. 3-4). Further, Alici teaches adding the concentration of NK cells to a bioreactor at a concentration of about 0.5×106 to about 2×106 cells/mL (i.e. 500,000-2million) (see e.g. para. 22 and 56), corresponding to the claim limitation of 1x106 cells/mL (i.e. 100,000-2million) and 0.7x106 cells/mL.
Furthermore, in regard to routine optimization, MPEP 2144.05(II)(A) states, “generally differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[W]here 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.’ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (‘It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.’)”. In the instant case, neither the specification nor Applicant have provided evidence that the claimed concentration of cells are critical, thus the teaching of about 0.5×106 to about 2×106 cells/mL (i.e. 500,000-2million) (see e.g. para. 22 and 56) as taught by Alici render the claimed cell concentration obvious.
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Min to incorporate the cell concentration and the step of inoculating a bioreactor with the cell culturing comprising NK cells that were obtained by stationary culture and then suspension culture as taught by Alici because Alici teaches methods for a closed system (i.e. bioreactor) for large scale expansion and simultaneous activation of natural killer (NK) cells (see e.g. para. 10). Incorporating the concentration of NK cells in the bioreactor as taught by Alici would have led to predictable results with a reasonable expectation of success because Min, which cites the prior art of Min 2013, discloses that it was known to produce NK cells with bioreactors (see e.g. pages 7-8). Further, Alici discloses that the bioreactor system has “shown suboptimal efficiency when started in low volumes and low cell numbers” (see para. 56). Further, Alici states that “the amount of cells in peripheral blood samples of donors does not allow directly starting in the bioreactor” (see e.g. para. 56). Additionally, as discussed above, Min cites the prior art of Min 2013 (WO2013094988A1) and discloses that reactors (i.e. bioreactors) are known for use in suspension culture methods with NK cell (see e.g. pages 7-8). Therefore, inoculating the bioreactor with the cell culture comprising NK cells that were obtained by stationary culture and then suspension culture, and incorporating the NK cell concentration as taught by Alici in the method of culturing NK cells as taught by Min would have led to predictable results with a reasonable expectation of success. Additionally, both Min and Alici teach obtaining an effective amount of NK cells to be used for therapeutic purposes (i.e. para. 10 and claim 23, respectively). Furthermore, an artisan of ordinary skill in the art of (i.e. NK cell culture methods) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claims 1, 15, and 17,, as discussed above, Min cites the prior art of Min 2013 (WO2013094988A1), which discloses that bioreactors are commonly used for suspension cultures (see e.g. pages 7-8).
Min is silent regarding the bioreactor’s pH, temperature, and agitation power, as discussed above.
However, as state supra, the prior art of Eibl discloses that bioreactors (e.g. Wave bioreactor) have essential parameters such as rocking rate, rocking angle, vibration frequency, temperature and aeration rate, which are adjustable (see e.g. abstract, page 58 and fig. 2). Further, Eibl discloses the bioreactors (e.g. Wave bioreactors as cited in the specification, see para. 56) have an agitation power per unit volume of 0.1-100 W/m3 (see e.g. pages 64-66, figs. 3-4), and temperature between 20-37°C (see e.g. page 62, fig. 2). Additionally, the prior art of Alici discloses that agitation and heating is at a temperature of about 36-40°C (see e.g. para. 16 and 57). Additionally, a person of ordinary skill in the arts could have arrived at the temperatures by routine optimization.
In regard to routine optimization, MPEP 2144.05(II)(A) states, “generally differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[W]here 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.’ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (‘It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.’)”.
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Min to incorporate the bioreactor temperature and agitation power as taught by Eibl and Alici because Eibl teaches that the bioreactor system setting can be adjusted and controlled (see e.g. abstract, page 58 and fig. 2). Incorporating the bioreactor settings as taught by Eibl and Alici with the methods of Min would have led to predictable results with a reasonable expectation of success because Min, Eibl, and Alici disclose culturing a suspension culture in a bioreactor (i.e. Wave bioreactor) was well a well-known technique. Therefore, a person of ordinary skill in the art would have incorporated the optimal bioreactor settings (i.e. temperature and agitation power), which would have led to predictable results with a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. suspension-culturing) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Eibl and Alici both do not explicitly state that the bioreactor is controlled to pH of 6.5-7.6.
However, the prior art of Somerville teaches the expansion of lymphocytes in a bioreactor (i.e. Wave bioreactor).
Regarding claims 1, 15, and 17,, Somerville discloses that the pH of the media was monitored daily throughout the duration of the expansion, which fluctuated within a narrow range around pH 7.2 (see fig. 1c), which reads on the claimed pH of about 7 (see e.g. page 3-4, fig. 1c).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Min with the pH range as taught by Somerville with a reasonable expectation of success. A person of ordinary skill in the art would have been motivated to do so because Somerville teaches that the bioreactor creates a more stable culture environment for rapidly expanding lymphocytes (see e.g. page 4, fig. 1 legend). As Min teaches that NK cells are known peripheral blood lymphocytes (para. 4) and Somerville teaches that the culture conditions for lymphocytes were more stable in the bioreactor (i.e. Wave bioreactor) (see e.g. page 4, fig. 1 legend), it would have been obvious to have the bioreactor control the pH with a reasonable expectation of success.
Regarding claim 2, Min teaches that cells can be cultured in suspension culture after 3-5 days (of stationary culturing) (see para. 89) or day 7 (see para. 94), which overlaps with the ranges as in claim 2 (MPEP 2144.05(I)).
Regarding claims 4-5, Min teaches that the methods can be performed in the presence of anti-CD3 antibodies OKT3, UCHT1, and HT3a (see e.g. claim 11, para. 56).
Regarding claim 6, Min discloses that the culturing of the step (a) is performed in a medium to which one or more cytokines selected from the group consisting of IL-2, IL-12, IL-15, Il-18, and IL-21 (see e.g. claim 12, para. 57) is added.
Regarding claim 7, Min teaches that the feeder cells may be inactivated T cells (i.e. a type of peripheral blood monocular cell (PBMC)) (see e.g. para. 53).
Regarding claim 8, Min discloses that the CD3-positive cells from the PBMC may be depleted (i.e. removed) (see e.g. page 4, paras. 19-27, 55; figs. 1-3).
Regarding claim 15, as discussed above, Min teaches a NK cell produced by the method according to claim 1 (see e.g. abstract, claim 1, paras. 11 and 88-95, figs. 1-5; Examples 1-2).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues that the combination of reference Min 2016, Min 2013, Eibl, Alici, Somerville do not teach or suggest every limitation of the amended claim 1 method. Further, Applicant asserts that the claimed parameters “significantly affect the result” (remarks, page 5-6) and cites Table 7, and Figure 7, which contain the optimal points of the bioreactor process parameters for maintaining the accumulated population doubling level (Remarks, page 6).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
Contrary to applicant's argument, the references of Min 2016, Min 2013, Eibl, Alici, Somerville do suggest every limitation of the amended claim 1, as discussed above.
In response to Applicant’s argument that the parameters significantly affecting the result (e.g. fig. 7), it is acknowledged that Table 7, recites a P value of 0.003, which is statistically significant (Remarks, page 6). However, it is not intuitive or clear how the parameters are significantly affecting the results to obtain the P value of 0.003. In response to Applicants’ argument, the data regarding the significantly effecting the results requires more of an explanation. As discussed above in the 112b rejections, the units, ratios, and target cell concentration are unclear. Therefore, the Examiner is not able to properly analyze the criticality in the parameters. It appears that Figure 7 does not have units present on the Y-axis (see figure below). Hence, it is unclear what the killing activity of the 10:1 and 3:1 represents in Figure 7. Furthermore, a ratio is known to be comparing two factors, such as cell populations. However, the claims and the specification do not recite what is being compared to in the ratios. Thus, it is not made clear as to what the ratio is made of in order to have the killing activity of the 10:1 and 3:1. As discussed above, it is unclear what the value of 73 and 93 refer to in claim 1, because there are numerous possibilities that the values may be referring too (e.g. bioreactor or cell population). Therefore, it is unclear what the values represent and what is being referring to in the claim. Hence, it is not clear to a person of ordinary skill in the art that there is enough information present to show that the parameters are significantly affecting the results.
[AltContent: textbox ([img-media_image1.png])]Furthermore, it appears that the specific parameters that Applicants refers to in Table 7 are referring to temperature, pH, inoculated cell concentration, and target cell concentration and the numbers of each parameter are predicted parameters (Spec. para. 39, 166). It is noted that the claim recites “about” for each of the parameters (i.e. temperature, pH, inoculated cell concentration, and target cell concentration). It is noted that the population doubling level appear to be temperature and pH dependent, and that at temperature of 37°C has decreasing killing activity at a titer of 10:1, and at a pH of 7.2 has decreasing killing activity at a titer of 3:1. Thus, the claim limitation of “the bioreactor is controlled to about pH 7 and culture temperature of about 36°C” would not be commensurate in scope with the claims. Furthermore, it is unclear if a person of ordinary skill in the art would be able to obtain the specific parameters without undue experimentation.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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.
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/ Examiner, Art Unit 1631
/JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631
Prosecution Insights