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, filed 4/30/2026, is acknowledged.
Claims 2-16, 25, and 26 are cancelled.
Claims 1, 17-24, and 27-30 are currently pending.
Newly added claims 29 and 30 do not recite the elected species of additional therapeutic, which is a chemotherapeutic drug.
Claims 18-24, 27, and 28 stand, and newly added claims 29 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions and/or Species.
Applicant has amended claim 17 to no longer recite the elected Species of cyclophosphamide. However, the elected genus of “chemotherapeutic drug” remains.
Claims 1 and 17 are under examination as reading on a pharmaceutical combination comprising an oncolytic virus and an IgG degrading enzyme, and the Species of a chemotherapeutic drug.
In view of the amendments and remarks filed on 4/30/2026, the following rejections remain.
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 and 17 stand rejected under 35 U.S.C. 103 as being unpatentable over Cerullo et al. (Mol Ther. 2011 Sep;19(9):1737-46. doi: 10.1038/mt.2011.113. Epub 2011 Jun 14, in Office Action mailed on 2/02/2026) in view of Majhen et al. (Hum Gene Ther. 2014 Apr;25(4):301-17. doi: 10.1089/hum.2013.235. Epub 2014 Mar 31, in Office Action mailed on 2/02/2026) and Leborgne et al. (Nat Med. 2020 Jul;26(7):1096-1101. doi: 10.1038/s41591-020-0911-7. Epub 2020 Jun 1, on IDS submitted 12/09/2025, in Office Action mailed on 2/02/2026), as evidenced by UnitProt entry Q7DAM2 (www.uniprot.org/uniprotkb/Q7DAM2/entry, sequence version 7/5/2004, in Office Action mailed on 2/02/2026).
Claims 1 and 17 stand rejected for the same reasons discussed in the Office Action mailed on 2/02/2026.
Applicant’s arguments and amendments, filed 4/30/2026, have been fully considered, but have been found to be not convincing.
Applicant argues: 1) The combination of Cerullo et al., Majhen et al., and Leborgne et al., does not teach or suggest the use of IdeS with oncolytic adenovirus type 5; 2) the combination of the references does not teach or suggest the use of the combination to treat lung cancer; 3) the disclosure and claims disclose unexpected results in treating lung cancer; and 4) Applicant has amended the claims to also recite the limitation of “IdeE”, which is not taught by the combined references. These arguments will be addressed individually below.
Applicant argues that the combined references do not teach or suggest the use of IdeS in a pharmaceutical composition with an Adv5 oncolytic virus.
This has been found to be not convincing. Applicant argues that the reference Leborgne et al. does not teach IdeS enzymatically digesting neutralizing antibodies against Adv5 viruses, only AAV viruses (Remarks pg. 11).
However, in response to applicant’s arguments against the references individually, one cannot show non-obviousness by attacking references individually where the rejections are based on combination of references. See MPEP 2145. Contrary to applicant’s arguments against the references individually, note that One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). See MPEP 2145 IV.
It is noted that in considering the disclosure of a reference, it is proper to take into account not only specific teaching of the reference but also the inferences which one skilled in the art would be reasonably be expected to draw therefrom In re Preda, 401 F.2d 825, 159 USPQ 342, 344 (CCPA 1968). See MPEP 2144.01.
Furthermore, specific statements in the references themselves which would spell out the claimed invention are not necessary to show obviousness, since questions of obviousness involves not only what references expressly teach, but what they would collectively suggest to one of ordinary skill in the art. See CTS Corp. v. Electro Materials Corp. of America 202 USPQ 22 (DC SNY ); and In re Burckel 201 USPQ 67 (CCPA). In re Burckel is cited in MPEP 716.02.
Here, given the teachings of Cerullo et al. teaching pharmaceutical compositions comprising Adv5 and cyclophosphamide, Majhen et al. providing motivation to include an agent that reduces the host immune response to Adv5, and Leborgne et al. teaching IdeS can block such an anti-viral immunogenic response by degrading host antibodies, the ordinary artisan at the time the invention was made would have had a reasonable expectation of success of making a pharmaceutical combination comprising Adv5, cyclophosphamide, and IdeS.
Additionally, one with ordinary skill in the art would appreciate that the IdeS enzyme functions on the host antibodies and not viruses. Applicant remarks (Remarks pg. 11): “…Leborgne only teaches IdeS for use in neutralizing anti-AAV antibodies and does not disclose or suggest that IdeS (or any other IgG-degrading enzyme such as IdeE) can degrade antiAd5 antibodies or function in the milieu of oncolytic adenoviral therapy.”
However, the antibodies that the instant specification discloses IdeS can degrade are the same antibodies taught by Leborgne et al. The instant specification discloses (Example 6): “…the mice were randomly divided into three groups, six mice in each group. On Day -1, blood was collected, and the human IVIg was injected intraperitoneally. 30 min after injecting human IVIg, the proteases were administered intravenously.” Also see Fig 8, disclosing that IVIg can neutralized Adv5:
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Leborgne et al. teaches that IdeS also degrades IVIg in vivo: “[t]he same experimental setting was applied to a therapeutically relevant mouse model of hemophilia B, where animals received an AAV8 vector expressing human coagulation factor IX (hFIX) following passive immunization with IVIg (Fig. 1c). In this setting, treatment with IdeS also resulted in the elimination of anti-AAV8 IgG and neutralizing antibodies…”
Therefore, the prior art teaches that IVIg can be degraded by IdeS in vivo, rescuing the effects (infectivity, etc.) of a virus that is also administered, whether it be Adv5 or AAV, particularly because the prior art teaches that IdeS acts by enzymatically degrading antibodies such as IVIg that are targeting the virus, and does not directly target the virus itself.
Applicant additionally argues that instant claim 1 has been amended to include the intended use limitation, and the combined reference do not teach the intended use of treatment of lung cancer.
This has been found to be not convincing. Obviousness can be established for achieving the claimed product for different reasons and the prior art/examiner does not need to know all of the properties of the claimed invention In re Dillon, 16 USPQ2d 1897 (Fed. Cir. 1990); however there must be some suggestion or motivation. Therefore, the reason or motivation to combine may often suggest doing what the inventor has done, but for a different purpose or to solve a different problem than that asserted by the inventor. See MPEP 2144.
Preamble language in claims of patents directed to administration of anticancer drug are expressions of purposes and intended results, and as such are non-limiting, since language does not result in manipulative difference in steps of claims; case does not present situation in which new use of process should be considered limiting because it distinguishes process over prior art and voluntary amendment adding preamble language, made after examiner indicated that claims were allowable, does not create material limitation.
It does not appear that the claim language or limitations result in a manipulative difference in the composition when compared to the prior art disclosure.
The Court held that the preamble language such as “for use in the treatment of lung cancer” was non-limiting and merely express a purpose of using the claimed pharmaceutical combination to treat lung cancer.
In re Hirao 190 USPQ 15, 16-17, (CCPA 1976) held that the preamble was non-limiting because it merely recited the purpose of the process, which was fully set forth in the body of the claim.
Here, the combined prior art references have arrived at the same composition, and in absence of evidence to the contrary Examiner asserts that the pharmaceutical composition taught by the combined prior art references can be used for the treatment of cancers such as lung cancer.
Applicant argues that the disclosure and claims disclose unexpected results in treating lung cancer, and remarks that Example 6 and Fig. 6 discloses this unexpected result. Additionally, applicant remarks that Fig. 8 discloses the unexpected result in treating lung cancer.
This has been found to be not convincing. Applicant has remarked about unexpected results as it pertains to a method of treating lung cancer in a subject. This does not apply to the composition recited in claims 1 and 17. Additionally, the prior art of Leborgne et al. teaches that IdeS can degrade IVIg to restore activity of a virus that has been administered to a subject (see supra), and thus this degradation of IVIg is an expected result.
Applicant further argues that the claims have been amended to recite IdeE in claim 1, and the combined references do not teach IdeE.
This has been found to be not convincing. The addition of the limitation of “IdeE” and specific IdeE sequences in claim 17 was incorporated via amendment, and the claim now recites “…IdeS or IdeE…”. The combined references still meet the claim limitations as teaching a pharmaceutical combination comprising an IdeS enzyme and cyclophosphamide.
Regarding the amendment to delete the limitation “cyclophosphamide”, instant claim 17 now recites “…wherein the pharmaceutical combination further comprises a targeted drug or a chemotherapeutic drug or an immune checkpoint blocker…the chemotherapeutic drug is selected from the group consisting of an immunosuppressant…”
However, Cerullo et al. teaches cyclophosphamide is a DNA alkylating chemotherapeutic agent with immunosuppressive activities (Introduction): “[c]cyclophosphamide (CP) is an alkylating agent that mediates DNA crosslinking and is used to treat various tumors. High doses are required for direct effects on tumor cells which results in immunosuppression.”, and therefore the claim limitations are still met.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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