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 .
Claim Status
Claims 1 – 21 are pending.
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.
Claims 1 – 5, 7 – 11, 14 and 17 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over Coffin (U.S. Patent Application No. US 2020/0199542 A1, cited on IDS), in view of Kozak et al. (U.S. Patent Application Publication No. US 2020/0190538 A1; hereinafter Kozak), and Evnin et al. (U.S. Patent Application Publication No. 2018/0057594 A1; hereinafter Evnin).
Regarding claims 1, 14 and 20, Coffin teaches a method for treatment of cancer in an individual in need thereof (claim 37). Claim 37 further discloses administering a therapeutically effective amount of the virus of any one of claims 1 to 24. Coffin discloses (paras. [0014] and [0016]) that the invention provides oncolytic viruses expressing genetic modifications: a fusogenic protein and at least one immune stimulatory molecule. Also, paragraph [0014] discloses that the oncolytic viruses of the invention provide improved treatment of cancer through improved direct oncolytic effects. Coffin does not teach an oncolytic double stranded RNA (dsRNA) virus, wherein the dsRNA virus is selected from Infectious Pancreatic Necrosis virus ("OV1") and Infectious Bursal disease Virus (IBDV) ("OV2").
Kozak discloses/provides motivation for utilizing modified oncolytic viruses for the treatment of cancer that includes Infectious Bursal Disease virus (para. [0012]; claim 4). Kozak further discloses that the modified avian virus exhibits oncolysis at higher temperatures (claim 3) than a non-avian oncolytic virus. Kozak further discloses (para. [0046]) the OV1 replicates within and induces the death of target cells (para. [0047]; cancer). Kozak discloses (para. [0024]) mammals as subjects for the study.
Evnin discloses pharmaceutical compositions (Abstract) containing a pseudotyped oncolytic virus and the delivery of therapeutic polypeptides that includes Infectious Pancreatic Necrosis virus (p. 11, para. [0113]; para. [0060}, viral-mediated destruction).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the viruses/motivation of Kozak’s and Evnin’s studies and combine the IBDV of Kozak, the IPNV of Evnin with the genetic modifications of Coffin, to provide novel oncolytic virus treatment options for treatment of cancer in an individual in need thereof.
Regarding claims 2 and 3, Coffin further teaches the OV1 or the OV2 comprises a genetic modification of its genome that enhances its oncolytic function. As stated in paragraph [0014], Coffin discloses that the invention provides oncolytic viruses expressing a fusogenic protein and at least one immune stimulatory molecule. Oncolytic viruses of the invention provide improved treatment of cancer through improved direct oncolytic effects, viral replication and spread through tumors, mediated by the fusogenic protein, which (i) increases the amount of tumor antigens, including neoantigens, which are released for the induction of an anti-tumor immune response; and (ii) enhances the expression of the virus-encoded immune stimulatory molecule(s). Expression of the immune stimulatory molecule(s) further enhances and potentiates the anti-tumor immune effect. Kozak discloses/provides motivation that the modified avian virus exhibits oncolysis at higher temperatures compared to a non-avian oncolytic virus (claim 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to understand Kozak’s disclosure that oncolytic avian viruses retain oncolysis at higher temperatures. It would be obvious to apply the same knowledge to Evnin’s cold-blooded fish virus of the same family.
Regarding claims 4, 5, 17 and 18, Coffin further teaches the genetic modification comprises a sequence encoding a therapeutic payload in claim 3 (Granulocyte-macrophage colony-stimulating factor (GM-CSF) included; claim 3 of Coffin).
Regarding claim 7, Coffin teaches the individual in need thereof is a mammal that is optionally a human or a canine. Coffin teaches specifically in paragraph [0008] as stated above, clinical trials involving human tumor tissue. Kozak discloses (para. [0024]) humans as subjects for the study.
Regarding claims 8, 9 and 19, Kozak discloses (para. [0046]) the OV1 replicates within and induces the death of target cells (para. [0047]; cancer). Kozak further discloses administering the OV to a subject with cancer (para. [0047]). ). Kozak discloses (para. [0024]) mammals as subjects for the study.
Regarding claim 10, Kozak discloses delivering an effective amount of the OV1 (para. [0044]).
Regarding claim 11, Evnin discloses administering a therapeutically effective amount of OV2 (para. [0016]).
Claims 6, 12, 13, 16 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Coffin, Kozak, and Evnin as applied to claims 1 – 5, 7 – 11, 14 – 15 and 17 – 20 above, and further in view of Brown (U.S. Patent Application No. 2005/0214316 A1, cited on IDS).
Regarding claims 6 and 16, Coffin in view of Kozak, and Evnin makes obvious the method of claim 2, yet does not expressly teach wherein the genetic modification comprises a disruption or mutation of a segment of the viral genome that encodes the viral VP5 protein such that the viral VP5 protein is not produced within cells infected with the OV1 or the OV2. Coffin does teach a genetic modification comprising a disruption or mutation of a segment of the viral genome with altered tropism. Coffin discloses (para. [0008]) that in herpes simplex virus (HSV) when only the ICP34.5 genes have been disrupted can replicate in many tumor cell types in vitro, and replicate selectively in tumor tissue, but not in surrounding tissue, in mouse tumor models. Clinical trials of ICP34.5 deleted, or ICP34.5 and ICP6 deleted, HSV have also shown safety and selective replication in tumor tissue in humans.
Brown teaches IBDV VP5 is a non-essential structural protein and that VP5 was the last IBDV protein identified (para. [0325]). This protein is not essential for IBDV replication in vitro or in vivo, however, it plays an important role in viral pathogenesis. It has cytotoxic properties and it may play a role in the release of the IBDV progeny.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the genetic modification could comprise a disruption or mutation of a segment of the viral genome that encodes the viral VP5 protein according to Brown, to potentially modulate its pathogenicity, and any altered host tropism according to Coffin.
Regarding claim 12, Brown teaches cDNA amplified from a segment of a genomic RNA of an OV. Brown discloses (para. [0054]) that in one embodiment, the sample is a paraffin embedded tissue sample. In an advantageous embodiment, IBDV cDNAs are generated by extracting RNA from the paraffin-embedded tissue sample and reverse transcriptase-polymerase chain reaction amplification of the IBDV cDNA with IBDV-specific primers. Brown further discloses (para. [0055]) that advantageously, the IBDV-specific primers amplify a hypervariable portion of IBDV, such as VP1, VP2, VP3, VP4 or VP5.
Regarding claim 13, Coffin in view of Kozak, Evnin, and Brown makes obvious the cDNA of claim 12, yet does not expressly teach cRNA transcribed from a cDNA. However, Brown teaches generating riboprobes from cDNA. Brown states in an advantageous embodiment (para. [0075]), the IBDV cDNA generated from the sample suspected of having IBDV is used as a probe to screen cDNA or genomic libraries specific to the sample to isolate a full-length clone corresponding to the novel strain of IBDV. Brown further (para. [0235]) discloses that using in situ hybridization staining with riboprobes specific for the VP2 gene of IBDV, no virus was detected in the proventriculi of 3 week-old chickens experimentally exposed to IBDV strain Delaware A and no histologically evident proventricular lesions were present.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the riboprobes comprise cRNA.
Regarding claim 21, Brown teaches one or more expression vectors encoding one or two segments of an OV in paragraphs [0099] and [0100].
Response to Arguments
Claim 15 is canceled.
Claims 1 – 21 were rejected under 35 U.S.C. 103. The rejection of claim 15 is canceled. The rejection of each remaining claim has been maintained and modified to include Kozak and Evnin. Kozak discloses the use of the Infectious Bursal disease virus for the treatment of cancer and Evnin discloses the use of the Infectious Pancreatic Necrosis virus for the treatment of cancer. Kozak and Evnin are edited in the rejections of claims 1 – 14 and 16 – 21. Caballero was removed from the rejections of claims 1 – 14 and 16 – 21. Brown was removed from the rejection of claims 1 – 5, 7 – 11, 14 and 17 – 20. However, Brown was maintained in the rejection of claims 6, 12, 13, 16 and 21.
Applicant argues that Coffin, Caballero, and Brown do not teach an oncolytic double stranded RNA (dsRNA) virus. The rejection has been edited to remove Caballero and replace Brown to include Kozak and Evnin. Kozak discloses the use of the Infectious Bursal disease virus for the treatment of cancer and Evnin discloses the use of the Infectious Pancreatic Necrosis virus for the treatment of cancer.
Applicant argues that Coffin is directed to a modified herpes simplex virus. The Examiner agrees that the virus is in a different class but the argument is not persuasive due to the modifications that Coffin used, such as a fusogenic protein and an immune stimulatory molecule, which can be applied to the oncolytic dsRNA viruses of Kozak and Evnin.
Applicant argues that Caballero describes empty virus shells assembled from the IBDV VP2 capsid protein and not the live virus. The rejections have been edited to remove Caballero and include Kozak and Evnin. Kozak discloses the use of the Infectious Bursal disease virus for the treatment of cancer and Evnin discloses the use of the Infectious Pancreatic Necrosis virus for the treatment of cancer.
Applicant argues that Brown discloses a diagnostic characterization method, not a therapeutic method. This argument is not persuasive because Brown still teaches generating IBDV cDNA (claim 12) and that IBDV VP5 (claim 6) is a non-essential structural protein that has cytotoxic properties and it may play a role in the release of the IBDV progeny. Also, Brown teaches generating riboprobes from cDNA (claim 13). It would be obvious to combine the knowledge taught from Brown on the characterization of IBDV with the oncolytic virus based cancer therapy treatment/methods/viruses of Coffin, Kozak, and Evnin.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached M-F 9:00A - 5:00P.
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/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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