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 .
Response to Amendment
The Amendment filed 09/09/2025 in which claims 1-6, 9 were amended, new claim 11 was added, has been entered.
Claims 1-11 are under examination on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 08/27/2025 after the Nonfinal Office Action mailed on 06/12/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Abstract
(Previous objection, withdrawn) Applicant’s amendments to the Abstract submitted on 09/09/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 06/12/2025.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 09/09/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 06/12/2025.
Claim Objections
(Previous objections, withdrawn as to claims 2-4, 9). Applicant’s amendments to claims 2-4, 9 have overcome previous objections to those claims.
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.
(Previous rejection, withdrawn as to claims 1-10) Claims 1-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to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.
See claims 1-10 as submitted on 09/09/2025.
Applicant’s amendments to claims 1-10, have overcome previous rejection to those claims.
(New rejection) Claim 11 is 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.
See claim 11 as submitted on 09/09/2025.
Claim 11 recites “wherein the amount of vaccinia virus harvested from the medium is greater than 300 TCID50/cell.” This statement is unclear because the term “TCID50” refers to the tissue culture infectious dose defined as that dilution of virus required to infect 50% of the cell monolayers in a plate. As such the TCID50 isn't directly "per cell" but represents the virus dilution (e.g., per mL) needed to infect 50% of cell monolayers in a plate. Instant Specification ¶ [0090] provides a correct explanation of the term “TCID50/mL”. However, the term “TCID50/cell” is not clear. Therefore the claim is indefinite.
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.
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.
(Previous rejection, maintained and modified as necessitated by amendment as to claims 1-10, expanded as to claim 11) Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Kirn et al. prior art of record.
See claims 1-11 as submitted on 09/09/2025.
Regarding amended claim 1, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 06/12/2025. No new limitations were introduced in the amendment filed on 09/09/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 06/12/2025 still applies to amended claim 1. As previously explained, Kirn et al. a method for the large scale production vaccinia virus (Abstract, ¶ [0007]), the method comprising the following steps:
(a) culturing suspended HeLa S3 cells (¶¶ [0045],[0075]);
(b) subculturing the suspended HeLa S3 cells and seeding at a density of
1.0 x 104 to 6.0 x 104 cells/mL (¶¶ [0075], [0081], [0082]); infecting the HeLa S3 cells with vaccinia virus at a multiplicity of infection (MOI) of between 0.01 and 0.03 TCID50/cell (¶¶ [0075], [0076], [0011]) and maintaining the HeLa S3 cells in culture for multiple days (¶¶ [0075], [0082]). Regarding the seeding density and MOI, it is noted that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
(c) harvesting the virus from the cell culture (¶ [0009], claim 1)
It would have been a matter of routine experimentation using standard laboratory techniques available before the effective filing date to determine the optimal seeding densities and MOIs as well as time intervals in culture to achieve high titers of viral particles with a reasonable expectation of success. Generally, differences in concentration or temperature 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). See also MPEP § 2144.05.
Accordingly, the limitations of amended claim 1 were prima facie obvious to one of ordinary skill in the art before the effective filing date especially in the absence of evidence to the contrary.
Regarding amended claims 2-4, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 06/12/2025. No new limitations were introduced in the amendment filed on 09/09/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 06/12/2025 still applies to amended claims 2-4. As previously explained, Kirn et al. disclose the method of claim 1 wherein the HeLa S3 cells are expanded before seeding and can be passaged multiple times (least 1, 2, 3, 4, 5, or more) and the time interval between passages can be between 2 and 4 days (¶¶ [0020] [0082]). It is noted that the number of passages as well as the time interval between passages are considered to be those determined by routine optimization according to one of skill in the art in view of the teachings of Kirn et al. (¶¶ [0020], [0081], [0082]).
Regarding amended claim 5, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 06/12/2025. No new limitations were introduced in the amendment filed on 09/09/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 06/12/2025 still applies to amended claim 5. As previously explained, as indicated above, Kirn et al. disclose a seeding density of 1.0 x l04 to 6.0 x l04 cells/mL (¶¶ [0075], [0081], [0082]). The seeding densities recited in claim 5 are considered to be those determined by routine optimization according to one of skill in the art in view of the teachings of Kirn et al. (¶¶ [0075], [0081], [0082]). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see MPEP 2144.05.01).
Regarding amended claims 6-8, it is noted that all of the amendments to claim 6 were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 06/12/2025. No new limitations were introduced in the amendment filed on 09/09/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 06/12/2025 still applies to amended claims 6-8. As previously explained, Kirn et al. further disclose wherein the HeLa S3 cells are cultured in a medium such as RPMI 1640 medium supplemented with 5% to 10% fetal bovine serum (FBS) (¶ [0014]) .
Regarding amended claim 9, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 06/12/2025. No new limitations were introduced in the amendment filed on 09/09/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 06/12/2025 still applies to amended claim 9. As previously explained, Kirn et al. further disclose a step of harvesting occurs 40-80 hours post infection which is approximately 2-4 days (¶ [0087]). Again, it is noted that the time interval from infection to harvest is considered to be those determined by routine optimization according to one of skill in the art in view of the teachings of Kirn et al. (¶ [0087]).
Regarding claim 10, as previously explained, Kirn et al. further disclose the method of claim 1 wherein the vaccinia virus is of the Western Reserve (WR) strain (¶ [0016], claim 25).
Regarding claim 11, Kirn et al. further disclose multiple amounts of harvested virus depending on cells and conditions (Fig. 1 ¶¶ [0045]-[0046]). The amount of virus harvested is considered to be one determined by routine optimization according to one of skill in the art in view of the teachings of Kirn et al. (Fig. 1 ¶¶ [0045]-[0046]). See MPEP 2144.05 Optimization Within Prior Art Conditions or Through Routine Experimentation.
Accordingly, it is herein maintained that claims 1-10 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 09/09/2025 have been fully considered but they are not persuasive.
Applicant contends on page 8 of the Remarks submitted on 09/09/2025:
Kim itself explicitly teaches that mass-producing vaccinia virus using a suspension culture method cannot be achieved. As shown in Fig. 1 of Kim, HeLa S3 cells in suspension produced well less than one virus particle per infected cell (i.e., 0.4 pfu/cell). Kim reasons that "it is possible that suspension cell cultures may be limited by poor cell to cell transmission of virus" ([0046]). Even when infecting HeLa S3 cells in suspension at the same MOI as recited in claim 1 (i.e., 0.01 to 0.1 TCID50/cell), Kim teaches that HeLa S3 suspensions were not effective for producing vaccinia virus (again see Fig. 1 and [0075]). In fact, Kirn fails to teach any method of culturing and infecting a human cell line that could be used for mass- production of the vaccinia virus given that even adherent HeLa cultures of Kirn were only capable of producing around 60 pfu/cells under optimal production conditions (see Fig. 1 and [0076]).
In response:
The instant rejection is in view of instant claim language. 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). Kirn et al. provide a teaching and suggestion of the use of suspended HeLa S3 cells as explained above in detail. While their yield might have been lower than when using adherent HeLa cells, it would have been a matter of routine experimentation using standard laboratory techniques available before the effective filing date to determine the optimal conditions to increase the yield with suspended HeLa S3 cells. Further, Kirn et al. provide a discussion of medium components and other factors that affect virus yield (see ¶¶ [0045]-[0046]). It is noted that the instant claims merely recite “mass-producing” which is considered production in large scale. Further, the instant claims recite “comprising” and are interpreted in an open-ended fashion and do not exclude additional components and/or steps (See MPEP 2111). It is maintained that in view of the language of the instant claims, one of ordinary skill in the art would have been motivated and had a reasonable expectation of success in arriving at the instant claims in view of the teachings and suggestions of Kirn et al.
Applicant contends on page 10 of the Remarks submitted on 09/09/2025:
As discussed above, Kirn fails to teach an effective method of mass-producing vaccinia virus using suspension cultures, let alone the effective use of suspended HeLa S3 and/or MDCK cell cultures. Again, Kirn is limited to the modest production (up to 60 pfu/cell) of vaccinia virus using adherent HeLa cell cultures. Kirn also teaches that productivity from adherent cultures is significantly better than all attempts at suspension cultures ([0047]) and that suspension cultures may be limited by poor cell to cell transmission ([0046]). Moreover, as explicitly disclosed in Kirn, the production of recombinant vaccinia virus (pfu/cell) in HeLaS3 suspension is nearly non-existent (i.e., 0.4 pfu/cell) even under perceived optimal conditions (see paragraph [0031] and Fig. 1).
The fact that HeLa S3 cells can be successfully cultured in growth medium and subsequently infected with vaccinia virus, as described in paragraphs [0045] and [0075] of Kirn, does not necessarily mean that such methods would be expected to be effective in a method for mass-producing vaccinia virus as recited in claim 1. Therefore, given the explicit teachings of Kirn regarding the failure of producing vaccinia virus using suspended cultures, it reasons that one having ordinary skill in the art would not look to use suspended cell cultures, such as HeLa S3 cells or MDCK cell cultures, in a method of mass-producing vaccinia virus as recited in amended claim 1.
In response:
The instant rejection is in view of instant claim language. It is noted that the instant claims 1-10 do not require any specific virus yield. 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). Kirn et al. provide a teaching and suggestion of the use of suspended HeLa S3 cells as well as an extended discussion of several optimization factors (see ¶¶ [0045]-[0046]) as explained above in detail. Applicant’s remarks in reference to the yield obtained by Kirn et al. is not relevant because, again, the instant claims do not require such a limitation. Accordingly, it is herein maintained that it would have been a matter of routine experimentation using standard laboratory techniques available before the effective filing date to determine the optimal conditions to increase the yield with suspended HeLa S3 cells and arrive at the claimed invention view of the teachings and suggestions of Kirn et al.
Conclusion
No claims are 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 MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J Visone can be reached at (571) 270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672