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 .
Claims Status
Amendments to the claims filed 07/17/2025 are acknowledged.
Claims 1-20, 31, and 32 were previously canceled.
Claims 21, 24-32, 34-37, 39, and 40 were cancelled in the claim amendments filed 07/17/2025.
Claims 22 and 38 are amended in the claim amendments filed 07/17/2025.
Claims 41-43 are newly added in the claim amendments filed 07/17/2025.
Claims 22, 33, 38 and 41-43 are pending and are examined on the merits.
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.
This is a new rejection as necessitated by the claim amendments.
Claims 22, 33, 38, 41, 42 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Tanabe et al (Proceedings of the 106th Annual Meeting of the American Association for Cancer Research, Vol 75, No. 15, August 1 2015; as cited in the IDS filed 07/17/2023) in view of Khuri et al (Journal of Clinical Oncology (2001)19:2;289-298), and Penheiter et al (Journal of Gene Medicine (2012) 14:590-597).
Regarding claim 22: The claim recites the terms “tail side of said tumor” and “mouth side of said tumor”. The instant specification is silent on an explicit definition for these terms. Figure 4 references the terms but does not clearly indicate the locations on a tumor. The art does not provide a specific definition of the terms.
For purposes of compact prosecution, the claim is interpreted as follows: "administration on opposing sides of the tumor, one side is towards the subject’s mouth and one towards the subject’s tail, or colon if tail is lacking".
Tanabe teach intratumoral needle injections of the oncolytic virus (an adenovirus) OBP-301 using a flexible endoscope (Title and Methods, Abstract p1 para 1/2). One of ordinary skill in the art would understand that an intratumoral needle injection using a flexible endoscope requires insertion of an endoscopic puncture needle filled with the oncolytic adenovirus-containing solution.
Tanabe do not teach the virus is administered to 5-10 sites in the tumor tissues and is silent on the specific location (e.g. periphery) on the tumor for viral administration. While Tanabe teach the dosage of viral particles administered, Tanabe does not teach the volume of the viral dosage that was administered. Tanabe do not teach the oncolytic virus is administered from a tumor margin on the tail side of said tumor to a tumor margin on the mouth side of said tumor. Tanabe do not teach the time for in injection is over 5 seconds.
Khuri teach intratumoral administration of the oncolytic adenovirus ONYX-015 (Title, p 290 para 1). For each patient, a single tumor is mapped into five equally spaced and equally sized section and ONYX-015 is injected into each of the five quadrants of the tumor (virus is administered to at least 5 sites in the tumor) (p291 para 2). The majority of the viral dose is administered at the tumor periphery (p291 para 2).
Khuri teaches a viral dose of 1x1010 particles (p 291 para 2). The volume of the viral dose taught by Khuri is at least 0.1 mL (Table 2).
It would have been prima facia obvious to one of ordinary skill in the art to include the injection volume taught by Khuri with the tumor injection method disclosed by Tanabe.
One of ordinary skill in the art would have been motivated to modify the method of Tanabe to include at least five additional sites of administration and include the peripheral base of the tumor as an administration site because Khuri teach and suggest that these are beneficial strategies to include when administering an oncolytic adenovirus to a tumor for therapeutic treatment. The optimization of the administered volume using the volume disclosed by Khuri as a starting point would have been obvious to the person of ordinary skill in the art in order to enhance the therapeutic treatment of the tumor. One of ordinary skill in the art would have had a reasonable expectation of success because the inventions are directed at treating solid tumors.
While Tanabe and Khuri do not teach the total volume of the solution containing the oncolytic virus is at least 1 mL, Khuri do teach that 0.1 ml is administered per tumor site, and therefore for 5 tumor sites require a total volume of 0.5 mL solution. If 10 tumor sites were injected at least 1 mL of solution would be required, and division of the tumor into injection sites would be a matter of routine optimization dependent on the size of the tumor.
Furthermore, the volume for injection is a matter of routine optimization based on the quantity of tumor sites being injected, the concentration of the viral particles, and protocols known in the art.
While Khuri do not explicitly teach injection of the tumor from a tumor margin on the tail side of said tumor to a tumor margin on the mouth side of said tumor, division of the tumor into at least 5 sections would result in an injection on opposing sides of the tumor, one side is towards the subjects mouth and one towards the subjects tail, or colon if tail is lacking.
Tanabe do not teach the time for injection for one tumor site is over at least 5 seconds. Penheiter teach delivery of an oncolytic virus to solid tumors (Title). 100ul of viral injectate is injected at a rate of 10 ul/s, for a total injection time of 10 seconds (p592 para 1).
It would have been prima facia obvious to one of ordinary skill in the art to modify the method of Tanabe, drawn to treatment of a tumor suing an endoscope by delivering the virus over 10 seconds, as taught by Penheiter.
One of ordinary skill in the art would have been motivated to do so because using a standardized injection rate would reduce variables in the treatment regime. One of ordinary skill in the art would have had a reasonable expectation of success because both inventions are directed to injecting oncolytic virus into solid tumors.
Regarding claim 33: The teachings of Tanabe are discussed supra. Tanabe also teach treatment of esophageal cancer (p1 para 1 abstract).
Regarding claims 38 and 42-43: The claim recites “one or more times”. The broadest reasonable interpretation of this claim is that the adenovirus is administered to multiple locations on the tumor, or administered over a multiple time periods.
Tanabe teach intratumoral injection of the tumor on days 1, 18, and 32 of treatment.
Regarding claim 41: The teachings of Tanabe are discussed supra. Tanabe also teach injection in patients with esophageal cancer (abstract).
Double Patenting
Applicant is advised that should claim 42 be found allowable, claim 43 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
This is a new rejection as necessitated by the claim amendments.
Response to Arguments
Response to Priority under 35 U.S.C. § 119:
Applicants’ submission of the certified priority document for application number 62847412 with a filing date of 14 May 2019 is acknowledged. Said document was filed with the instant Application on 11/12/2021.
Response to Information Disclosure Citation:
The Information Disclosure Statement filed on May 22, 2025 has been considered, please see documents filed with this action.
Response to Objection to the Abstract of the Disclosure:
The Abstract was objected to because it contained more than one paragraph. The Abstract filed 07/17/2025 comprises a single paragraph and thus overcomes the objection. The objection is withdrawn.
Response to Rejection under 35 U.S.C. § 102:
Applicant’s arguments, see p7, filed 07/17/2025 , with respect to the rejection(s) of claim(s) Claims 21, 22, 23, 28, 29, 30, 33, 38, 39 and 40 are rejected under 35 U.S.C. 102(a)(l) and 102(a)(2) as being anticipated by Tanabe et al (Proceedings of the 106th Annual Meeting of the
American Association for Cancer Research, Vol 75, No. 15, August 1 2015) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made under 35 U.S.C. § 103 in view of Tanabe et al (Proceedings of the 106th Annual Meeting of the American Association for Cancer Research, Vol 75, No. 15, August 1 2015; as cited in the IDS filed 07/17/2023) in view of Khuri et al (Journal of Clinical Oncology (2001)19:2;289-298), and Penheiter et al (Journal of Gene Medicine (2012) 14:590-597).
Response to Arguments for Rejection under 35 U.S.C. § 103:
Applicant’s arguments filed 07/17/2025 have been fully considered but they are not persuasive.
Applicant argues “the present invention is characterized in that a drug is mainly injected into a gastrointestinal cancer using an endoscope.” (p8 ¶4).
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., gastrointestinal cancer) are not recited in the rejected claim 22. 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).
Thus this argument is found unpersuasive.
Applicant argues Penheiter is drawn to murine tumors and is therefore not applicable to human tumors (p11 ¶5).
This is not found persuasive as use of animal models is standard practice when developing human treatments.
Applicant argues that Khuri “teaches away” from the present invention (p9 ¶2). However support for this assertation is not found and therefore the argument is mere allegation and therefore unpersuasive.
Applicant argues neither Tanabe nor Khuri teach administration of an oncolytic adenovirus-containing solution to the "peritumoral region and/or the margin of tumor tissue" and that this feature is essential to the instant invention (p10 of Remarks).
It is noted that “peritumoral region” is not found in the instant claims, but this is considered to read on peripheral base of the tumor. The instant claim 22 recites “the oncolytic adenovirus is administered to the peripheral base of the tumor and/or the marginal region of the tumor”.
Khuri teach the majority of the viral dose is administered at the tumor periphery (p291 para 2) as discussed in both the current and previous actions. Furthermore, as discussed in the instant action, while Khuri do not explicitly teach injection of the tumor from a tumor margin on the tail side of said tumor to a tumor margin on the mouth side of said tumor, division of the tumor into at least 5 sections (as taught by Khuri) would result in injection on opposing sides of the tumor including one side towards the subjects mouth and one towards the subjects tail, or colon if tail is lacking.
Thus the argument is not persuasive.
Applicant argues against Penheiter because of the type of oncolytic virus disclosed by Penheiter differs from that of the present invention (p11 ¶2). This is not found persuasive because the aspect of Penheiter that is relied on is the injection parameters, not the solution of oncolytic virus.
Furthermore, MPEP 2144.06 states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art."
It is by definition a prima facie case of obviousness to combine features of inventions drawn to injection of solid tumors when both inventions are shown to be successful.
Applicant refers to Yano to support differences in low does and high dose administration of virus, and Yano has been fully considered. Yano is silent on injection rate and injection volume and is not found to relevant to the merits of Penheiter.
These arguments are unpersuasive.
Response to Arguments for Double Patenting:
Cancellation of claim 21 overcomes the rejection under double patenting stated in the action mailed 04/18/2025 and the previous rejection is withdrawn.
Please note a new double patenting rejection is required by the claim amendments filed 07/17/2025 and is discussed supra.
Conclusion
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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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631