DETAILED ACTION
Applicant’s response filed January 12, 2026 has been received and entered into the application file. Applicant’s arguments and amendments to the claims have been fully considered.
Claims 1-11 and 14-15 of the claim set filed January 12, 2026 are pending. Claims 3-7 and 14 are withdrawn. Claims 12-13 are cancelled. Thus, claims 1-2, 8-11 and 15 are being examined on the merits herein.
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 .
Objection(s)/Rejection(s) Withdrawn
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1-2, 8-11, 13 and 15 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. Claims 2, 8-11, 13 and 15 are rejected by virtue of their dependency on claim 1 and for not rectifying the issue at hand.
Applicant amendment removed the phrases “enhanced” [proliferative ability] and “minimal loss” [of virus proliferative ability]. As such, the previously filed rejections are withdrawn.
Rejection(s) Maintained & Updated for Amendment
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
RE: Rejection of Claims 1-2, 8, 10, 13, and 15 under 35 U.S.C. 103 as being obvious over Kumamoto in view of Chen.
RE: Rejection of Claims 9 and 11 under 35 U.S.C. 103 as being obvious over Kumamoto in view of Chen and Gu.
Applicant amendment has cancelled claim 13 thus making the rejection of said claim moot.
Applicant amended claim 1 to now state: A method for expanded proliferation of a microorganism that infects monocytes or dendritic cells, comprising:
infecting a monocyte to which a cMYC gene, and at least one gene selected from a BMI1 gene, an EZH2 gene, an MDM2 gene, an MDM4 gene, an HIF1A gene, a BCL2 gene, and an LYL1 gene have been introduced, or a dendritic cell which has been introduced to be differentiated from the monocyte with the microorganism; and
culturing the infected monocyte or the infected dendritic cells for 24 to 96 hours allowing the microorganism to proliferate;
wherein the infectious microorganism is a dengue virus.
Thus, Applicant amendment has changed the scope of the claims from a method for expanded proliferation of monocytes or dendritic cells infected with a microorganism to a method for expanded proliferation of a microorganism that infects monocytes or dendritic cells.
However, Examiner respectfully notes Applicant’s amendment is not sufficient to overcome the previous rejection of record. Said amendment is merely de minis as the prior art teaches the same cells (i.e., Kumamoto) infected with dengue virus (i.e., Chen) as the instant claim. Thus, as is discussed below in the rejection of claim 1, now updated due to Applicant amendment, the prior art teaches the same method steps of infecting with dengue virus (i.e., Chen) a monocyte expressing the genes required by claim 1 (Kumamoto) and further teaches a culturing time which falls within the claimed range of culturing time of amended claim 1 (i.e., Chen). In addition, Examiner respectfully notes the prior art teaches (i.e., Chen) that kinetic studies showed that intracellular and extracellular infectious viruses were synthesized and released after 12 h of infection, followed by a log phase of growth, and peak viral yields were detectable at about 36 to 48 h postinfection (Fig. 3A; p9880 2nd column 1st paragraph).
Thus, the method disclosed by the prior art (i.e., Chen in combination with Kumamoto) would necessarily result in expanded proliferation of a microorganism, i.e., dengue virus, that infects monocytes or dendritic cells when cultured for 36 to 48 hours post infection, i.e., a time period falling within the claimed culturing time of claim 1.
As such, the previous rejection of record teaches the amended claim limitations and therefore the previous rejection of record is maintained.
The rejection of claims 1 and 2 below has been updated due to Applicant amendment. As no other claim amendments have been made, for ease of viewing, Examiner has copied the previously filed rejections of claims 8-11 and 15 from the OA filed April 4, 2024. Additionally, as the teachings of Kumamoto encompass the limitations required by claim 15 (i.e., the required genes), the rejection of claim 15 has been included with the rejection of amended claims 1 and 2 below.
Claims 1-2, 8, 10, and 15 are rejected under 35 U.S.C. 103 as being obvious over Kumamoto in view of Chen.
In regards to claims 1,2, and 15, Kumamoto teaches an improved method for inducing proliferation of monocytes derived from human peripheral blood comprising introducing into said monocytes at least three genes: cMYC, BMI1, and BCL2 or LYL1 gene (i.e., claim 15) (Abstract and [0014]). Kumamoto further teaches of a method for producing a dendritic cell from monocytes derived from human peripheral blood comprising introducing into said monocytes at least three genes: cMYC, BMI1, and BCL2 or LYL1 gene and inducing differentiation into dendritic cells by culturing the monocyte having the proliferative ability together with a differentiation inducing factor ([0014]). Thus, Kumamoto teaches enhanced proliferative ability of monocytes into which at least three genes, i.e., cMYC, BMI1, and BCL2 or LYL1 gene, have been introduced.
Kumamoto does not teach of infecting said cells with dengue virus.
Chen teaches of infecting blood monocytes with dengue virus and further teaches dengue virus primarily infects blood monocytes (Abstract and p9879, 2nd column, “Infection of MO with DV”). Chen further teaches of culturing said monocytes. Specifically, Chen teaches for long term cultures, monocytes were incubated with dengue virus inoculum for 2.5 hours to permit viral absorption. Thereafter, the unabsorbed viruses were removed and the dengue virus infected monocyte cultures were further incubated for 40 to 48 hours or the time periods indicated (p9879, 2nd column, “Infection of MO with DV”). Chen additionally teaches that kinetic studies showed that intracellular and extracellular infectious viruses were synthesized and released after 12 h of infection, followed by a log phase of growth, and peak viral yields were detectable at about 36 to 48 h postinfection (Fig. 3A, 3B; p9880 2nd column 1st paragraph). Thus, Chen teaches a method for proliferation of dengue virus infected monocytes with peak viral yield at about 36 to 48 hours postinfection. Examiner respectfully notes the long-term culture time of Chen, i.e., 36 to 48 hours, falls within the claimed range of culture time of the instant claim 1, i.e., 24 to 96 hours. Furthermore, Chen teaches that terminally differentiated monocytes, i.e., dendritic cells, cultured from more than 45 days could support productive dengue virus infection (Abstract, Fig 2).
Fig 3A and 3B Chen
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Fig 2 Chen
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Therefore, Chen has established a method of proliferating dengue virus via infection of monocytes and importantly teaches dengue virus primarily infects monocytes.
Chen does not teach introducing the required genes into said monocytes.
Thus, Kumamoto teaches of an improved method for inducing proliferation of monocytes and dendritic cells derived from peripheral blood. Chen teaches dengue virus primarily infects monocytes and teaches a method of proliferating said virus within monocytes. Therefore, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to combine the teachings of Kumamoto and Chen in order to have an improved method for proliferating monocytes (via the teachings of Kumamoto) into which dengue virus could be infected and thus have expanded proliferation (i.e., the teachings of Chen). A POSITA would have been so motivated to combine said teachings due to Chen teaching dengue virus primarily infects monocytes. One of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Kumamoto and Chen due to both being in the field of cell therapy.
Thus, the claims are obvious and are properly rejected.
In regards to claim 8, Kumamoto and Chen teach the method of claim 1. Further, Kumamoto teaches wherein the monocytes are isolated from human peripheral blood ([0020]).
Thus, the claim is obvious and is properly rejected.
In regards to claim 10, Kumamoto and Chen teach the method of claim 1. Further, Kumamoto teaches wherein the monocytes are prepared by isolating said monocytes from human peripheral blood ([0020]).
Thus, the claim is obvious and is properly rejected.
Claims 9 and 11 are rejected under 35 U.S.C. 103 as being obvious over Kumamoto in view of Chen and Gu.
In regards to claim 9, Kumamoto and Chen teach the method of claim 8. Further, Kumamoto teaches wherein the monocytes are prepared by isolating said monocytes from human peripheral blood ([0020]).
Kumamoto and Chen do not teach wherein the human pluripotent stem cell is an iPS cell.
However, as is known in the art and taught by Gu, induced pluripotent stem cells (iPS) cells are generated from human peripheral blood. As is further known in the art and taught by Gu, the generation of said iPS cells provides a convenient and low-invasive way to obtain iPS cells (Abstract). Gu additionally teaches of optimized mononuclear cell (i.e., monocyte) isolation and cultivation from human iPS cells (Methods).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to do a simple substitution of one known element for another to obtain predictable results. It would have been obvious to substitute monocytes from human peripheral blood as taught by Kumamoto for monocytes from induced pluripotent stem cells (iPS) cells as taught by Gu in order to have a convenient and low-invasive way to obtain monocytes.
The skilled artisan would have had a reasonable expectation of successfully substituting monocytes from human peripheral blood as taught by Kumamoto for monocytes from induced pluripotent stem cells (iPS) cells as taught by Gu. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Thus, the claim is obvious and is properly rejected.
In regards to claim 11, Kumamoto and Chen teach the method of claim 10. Further, Kumamoto teaches wherein the monocytes are prepared by isolating said monocytes from human peripheral blood ([0020]). Kumamoto and Chen do not teach wherein the human pluripotent stem cell is an iPS cell.
However, as is known in the art and taught by Gu, induced pluripotent stem cells (iPS) cells are generated from human peripheral blood. As is further known in the art and taught by Gu, the generation of said iPS cells provides a convenient and low-invasive way to obtain iPS cells (Abstract). Gu additionally teaches of optimized mononuclear cell (i.e., monocyte) isolation and cultivation from human iPS cells (Methods).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to do a simple substitution of one known element for another to obtain predictable results. It would have been obvious to substitute monocytes from human peripheral blood as taught by Kumamoto for monocytes from induced pluripotent stem cells (iPS) cells as taught by Gu in order to have a convenient and low-invasive way to obtain monocytes.
The skilled artisan would have had a reasonable expectation of successfully substituting monocytes from human peripheral blood as taught by Kumamoto for monocytes from induced pluripotent stem cells (iPS) cells as taught by Gu. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Thus, the claim is obvious and is properly rejected.
Response to Remarks/Amendment
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37 CFR 1.132 Declaration
RE: Rejections under 103 and the Declaration under 37 CFR 1.132
The examiner acknowledges receipt of the Declaration under 37 CFR 1.132 by Kazuo Miyazaki filed on 1/12/2026.
The Declaration under 37 CFR 1.132 filed 1/12/2026 and Applicant remarks filed 1/12/2026 have been carefully considered but have not been found persuasive.
Examiner thanks Applicant for the improved translation paragraphs of Kumamoto.
Examiner respectfully notes Applicant remarks (p9) in regards to the field, description and purpose of the cited art. Examiner notes Applicant remarks state at the time of the invention, dengue virus was conventionally propagated in other cell types, such as Vero and mosquito cells and that monocytes were not recognized as standard hosts for high titer dengue virus production capable of repeat passages. Further, Examiner notes Applicant remarks state that although Chen taught monocytes can be infected with dengue virus, such monocytes were used merely as a model to study immune responses and were not suitable as host cells for an expanded proliferation culture of dengue virus.
In response, Examiner respectfully submits that Chen teaches culturing within the claimed culture times of claim 1 and further teaches dengue virus had expanded proliferation within said culture time. Please see the rejection of claim 1 above.
Further, Examiner respectfully notes that Applicant remarks state Kumamoto is directed to growing monocyte-lineage cells and using them as an in vitro tool for infectious microorganism research and vaccine production.
In response, Examiner respectfully notes Kumamoto teaches an improved method for proliferation of monocytes and as Chen teaches infecting monocytes with dengue virus and teaches monocytes preferentially infect monocytes, a POSITA would thus be motivated to combine the teachings of Kumamoto and Chen in order to have proliferative monocytes in which to infect with dengue virus.
Additionally, Examiner notes Applicant remarks (p10) state “Rather than seeking to establish a practical system for sustained virus propagation and repeat culturing in human cells, Kumamoto and Chen focus on immune induction, antigen presentation or analysis of host immune responses…”
In response, Examiner respectfully notes Chen teaches the same culturing times as the instant claim 1 and additionally teaches the virus propagated within said culture time.
Examiner notes Applicant remarks (p11) state “… the teachings of Kumamoto regarding immune-induction use of dendritic cells do not address-nor would they have reasonably suggested-conditions for maintaining culture that enables expanded proliferation and repeated passaging of dengue virus as claimed in the instant application.”
In response, Examiner respectfully notes Chen teaches the same culture time, and virus expansion within said culture time of dengue virus infected monocytes, and due to Kumamoto teaching monocytes with improved proliferation, a POSITA would have been motivated to combine the teachings of Kumamoto and Chen in order to have more proliferative monocytes in which to infect with dengue virus for the claimed culture time of claim 1.
Examiner notes Applicant remarks (p11-12) state Kumamoto teaches away from the Applicant’s invention. Examiner respectfully disagrees. As Kumamoto teaches expanded monocyte proliferation and Chen teaches dengue virus proliferation within the claimed culture time, a POSITA would have been motivated to combine the teachings of Kumamoto and Chen in order to have more proliferative monocytes in which to infect with dengue virus for the claimed culture time of claim 1.
In regards to Applicant remarks stating Chen studies cytokine and chemokine production on transient dengue virus infection of primary monocytes in vitro to analyze immune responses, Examiner respectfully notes Chen teaches dengue virus proliferation within the claimed culture time.
Thus, in response to “Consequently neither reference individually or combined discloses, teaches or suggests expanded viral proliferation in infected monocytes or dendritic cells,” Examiner respectfully disagrees based on the foregoing analysis and the updated rejection of claim 1.
Examiner notes Applicant remarks in regards to lack of reasonable expectation of success (p13). In particular, Examiner notes Applicant remarks stating “Thus a person of skill in the art would not have reasonably expected or predicted that simply immortalizing monocytes (as in Kumamoto) and infecting them with dengue virus (as in Chen) would yield the specific, stable, high-output dengue proliferative system of the present invention.” Examiner respectfully notes however, as discussed above, that Chen teaches virus proliferation within the claimed culture times. Thus, Chen teaches a specific, stable, high-output dengue proliferative system as is currently claimed in claim 1.
Examiner respectfully believes the above remarks sufficiently address all points brought forth by the Applicant in both the affidavit filed 1/12/2026 and the Applicant remarks filed the same date.
Conclusion
No claims are allowable. No claims are free of the prior art.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
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/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633