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
Applicant's amendment and argument filed 09/04/2025, in response to the non-final rejection, are acknowledged and have been fully considered. Any previous rejection or objection not mentioned herein is withdrawn.
Claims 1-2, 4-6, 8-9, 12-15, 19-27 are pending and being examined on the merits.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 4-6, 8-9, 12-15, 19-27 are rejected under 35 U.S.C. 103 as being unpatentable over Brian Goodman and Jason Hudak (from IDS, WO2019023555A1), hereinafter Goodman and William Parker and Eric Sorscher (IN2013DN08151A), hereinafter Parker. This rejection is maintained due to the amendments and arguments filed on 09/04/2025.
Regarding claims 1, 19-20 and 22 Goodman teaches methods for treating or preventing a disease or condition comprising administering to a subject (e.g., a human subject) a composition provided herein. In some embodiments, the disease or condition is a cancer (see 0003). Goodman teaches administering compositions which comprise of a polymer covalently attached to a residue of a therapeutic agent (see claim 22), wherein the therapeutic agent is checkpoint inhibitor (see claim 27), and wherein this is in combination with a prodrug enzyme which can be a purine nucleoside phosphorylase, and delivery of a prodrug (e.g., 6-methylpurine 2'-deoxyriboside) (see 0120-0121 and 0145). Goodman teaches wherein the checkpoint inhibitor inhibits CTLA4, and PD-L1 (see 0077) and teaches the use of fludarabine (see claim 25 or 0075) which is the active chemotheraputic agent being claimed (F-ara-AMP).
Regarding claim 2, Goodman also teaches injection into tumor as forms of administration (see 0240-0241).
Regarding claims 8-9, Goodman teaches wherein the checkpoint inhibitor is a biologic therapeutic or small molecule and a monoclonal antibody, such as Nivolumab (BMS, anti-PD-1), Pembrolizumab (Merck, anti- PD-1), Ipilimumab (BMS, anti-CTLA-4), MEDI4736 (AstraZeneca, anti-PD-Ll), and MPDL3280A (Roche, anti-PD-Ll) (see 0076).
Regarding claims 12 and 19, Goodman teaches wherein the anticancer compound can be Ipilimumab, (see 0089, 0092).
Regarding claim 13, Goodman teaches in some embodiments, the methods and compositions provided herein relate to the treatment of a leukemia, such as chronic lymphocytic leukemia (see 0159).
Regarding claims 14-15, Goodman teaches wherein the cancer being treated can be breast and colon cancers (see 0158).
Regarding claim 21, Goodman teaches wherein nivolumab and pembrolizumab are the PD-1 inhibitors (see claim 30).
Regarding claim 24, Goodman teaches wherein the cancers are head and neck cancer (see 0010).
Regarding claim 25, Goodman teaches wherein treatments are targeted to oral squamous cell carcinoma which is a type of head and neck cancer.
Regarding claim 26, Goodman teaches in some embodiments that radiation may be administered in conjunction with the treatment (see 0146).
Regarding claim 27, Goodman teaches human subjects (see summary, 0001 and 0024).
Goodman does not specifically teach wherein the purine nucleoside phosphorylase is non-mammalian and wherein administering is a direct injection into replicating or non-replicating targeted cells and optionally exposure of the targeted cells to X-ray radiation. Goodman does teach injection into tumors which with the broadest reasonable interpretation would both be replicating and non-replicating cells depending on the tumor type.
Parker’s general disclosure is to enhanced therapeutic usage of a purine nucleoside phosphorylase or nucleoside hydrolase prodrug related applications (see abstract).
Regarding claims 1-2 and 4-5, Parker teaches “Use of a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression thereof, and a prodrug cleaved by said purine nucleoside phosphorylase or nucleoside hydrolase for the preparation of a direct injection medicament for the functional inhibition or killing of replicating or non-replicating targeted cells” (see claim 1). Parker teaches wherein the purine nucleoside phosphorylase is from E. coli and wherein the PNP gene has been shown to generate highly potent compounds such as 2fluoroadenine (F-Ade) or 6-methylpurine (MeP) intratumorally (see 0006).
Regarding claim 6, Parker teaches “it is further appreciated that mutant PNPs and hydrolases such as those detailed in US 7,488,598 are operative herein to generate a cytotoxic purine base from the prodrug and suitable for inhibiting cellular function such as reproduction and even killing of those cells of a human subject that have been transfected or are simply in proximity to the enzyme” (see 0033).
Therefore, it would have been obvious to persons having ordinary skill in the art before the effective filing date to use a non-mammalian purine nucleoside phosphorylase such as one from E. coli in the invention taught by Goodman, because as Parker teaches that the PNP gene from E. coli has been shown to generate highly potent compounds such as 2fluoroadenine (F-Ade) or 6-methylpurine (MeP). Parker and Goodman both teach that the method is directed to treating cancer and is directed to use of the same components. Combing knowledge from both of these related pieces of art into a single method for treating cancer would have been prima facie obvious. The use of X-ray radiation in conjunction with the treatment would have been obvious given that Goodman teaches the use of radiation in conjunction with treatment. X-rays are a form of radiation and is known to cause damage to or destroy cancer cells by breaking down their DNA which prevents them from growing and dividing.
There would have been a reasonable expectation of success in arriving at the instant invention because both pieces of art are related and teach treating cancer with the use of administering purine nucleoside phosphorylases and a prodrug cleaved by the purine cleaving enzyme. Administering effective amounts of a checkpoint inhibitor would have been obvious as there are known anticancer checkpoint inhibitors as can be appreciated from the relied upon art.
Response to Arguments
Applicant's arguments filed 09/04/2025 have been fully considered but they are not persuasive. The applicant argues that claims are not obvious because Goodman merely teaches that the checkpoint inhibitors exist and that does not teach or suggest using immune checkpoint inhibitors for treatment of cancer in combination with a non-mammalian purine nucleoside phosphorylase or a vector encoding non-mammalian purine nucleoside phosphorylase and fludarabine phosphatase. This however is not the case as can be appreciated from the above rejection. The combination of those treatments is obvious given the prior art. The applicant argues that Parker does not teach the same as what was just argued. Both Parker and Goodman teach the claimed invention and with their combined art make the instant invention obvious as just discussed in the above rejection. Using checkpoint inhibitors as a means of cancer treatment, especially the ones being claimed, along with purine nucleoside phosphorylases is prima facie obvious given the prior art.
Conclusion
Currently 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 JACOB ANDREW BOECKELMAN whose telephone number is (571)272-0043. The examiner can normally be reached Monday-Friday 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Terry McKelvey can be reached at 571-272-0775. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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JACOB A BOECKELMAN Examiner, Art Unit 1655
/TERRY A MCKELVEY/ Supervisory Patent Examiner, Art Unit 1655