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 1-17 of record 3/15/24 are pending and subject to prosecution. Prosecution on the merits commences for claims 1-17.
PRIORITY
The instant application filed 3/15/2024, is a CONTINUATION of US Patent No. 11,963,990 filed 05/24/2023, which is a CONTINUATION of US Patent No 12,016,893, filed 12/13/2022, which is a CONTINUATION of PCT/US2022/026703, filed 04/28/2022, which claims priority to US Provisional Application No. 63/182,243, filed 04/30/2021. Thus, the earliest possible priority for the instant application is 4/30/2021.
CLAIMS
Independent claim 1 is directed to an oncolytic virus, wherein the oncolytic virus comprising an insertion of an exogenous nucleic acid encoding for a modified CXCR4, wherein the modified CXCR4 comprises an amino acid substitution at a position corresponding to Y157 of SEQ ID NO: 20.
The broadest reasonable interpretation of a modified CXCR of claim 1, wherein, “the modified CXCR4 comprises an amino acid substitution at a position corresponding to Y157 of SEQ ID NO: 20” does not require the CXCR4 comprise the full-length sequence of SEQ ID NO: 20. The claimed phrase encompasses any CXCR4 protein comprising any two consecutive amino acids encoded by SEQ ID NO: 20, so long as a CXCR4 protein comprises a tyrosine residue that “corresponds” to a tyrosine at 157 of SEQ ID NO:20.
In addition, the recitation of claim 3 of “wherein the modified CXCR4 comprises an amino acid sequence of SEQ ID NO: 18” does not require full-length SEQ ID NO:18. Use of “an” amino acid sequence encompasses any CXCR4 protein comprising any two consecutive amino acids encoded by SEQ ID NO: 18. Amendment to recite “wherein the modified CXCR4 comprises the amino acid sequence of SEQ ID NO: 18” would require full-length SEQ ID NO:18.
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.
Claim 7 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.
Claim 7 is rejected for the use of parentheticals. Claim 7 recites ”a Western Reserve strain Vaccinia virus (ATCC VR-1354)” “a Wyeth strain (ATCC VR-325)”and “an Ankara strain (ATCC VR-1508 or ATTC VR1566)”. There are more western reserve strains, wyeth strains, Ankara strains of virsuses than those specific strains encompassed within the parentheticals. Thus, it is unclear whether the claim requires those specific strains identified by accession number, or if they are exemplary. See MPEP § 2173.05(d).
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.
Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/089755 A1 to Thorne, of record, cited on Applicant’s IDS dated 4/02/2024, further in view of US Patent Application Publication No. 2019/0142883 to “Thorne-2”, UniPro entry P61073 for CXCR4 downloaded from https://www.uniprot.org/uniprotkb/P61073/entry#sequences on 6/27/2026, and Denizot et al 2008.
The applied WO 2019/089755 Thorne and US Patent Application Publication No. 2019/0142883 to “Thorne-2”references have a common inventor with the instant application. Based upon the earlier publication date of the references, they constitute prior art under 35 U.S.C. 102(a)(1). The earliest priority date for the instant application is 4/30/2021. Thus, the 1-year exceptions provided for under 35 USC 102(b)(1) extend to 4/30/2020. As such, the exceptions provided for under 35 USC 102(b)(1) are not available to overcome any rejection based on this reference. See, generally MPEP § 717.02.
With regard to claim 1, Thorne discloses recombinant oncolytic viruses which encodes an exogenous nucleic acid encoding a chemokine receptor, wherein the chemokine receptor is CXCR4, wherein the CXCR4 is inserted into the oncolytic viral genome (see, Abstract, paragraphs [0003]-[0004], [0009]-[0038], [0042]-[0043], [0047]-[0070], [0072], [0080]-[0083], [0125]-[0150], [0155]-[0158], [0166]-[0172], [0180]-[0182], [0185]-[0190], [0194]-[0204], and [0209]-[0237]; Example 2; Example 5; Example 6; Example 8). The amino acid sequence of CXCR4 of Thorne is a human CXCR4 (SEQ ID NO: 110). Thorne discloses the oncolytic viruses encoding chemokine receptors can be administered systemically, and expression of the chemokine receptor enhances systemic delivery of the virus (paragraph [0042]). Thorne discloses oncolytic viruses expressing chemokine receptor CXCR4 administered systemically infect lymphocytes such as B cells, and can re-direct the infected B-cells to tumors expressing the cognate cytokine CXCL12, results in significantly increased viral load in the tumor, and/or boosted immune responses to tumors infected with the virus (paragraphs [00187], [00189], [00190], [00192]). Thorne discloses the CXCR4 peptides can be modified (paragraphs [00185]-[00186], [00192], [00219]). Thorne discloses the oncolytic viruses can encode nucleic acids which modulate STAT3-mediated gene activation (paragraph [0047], [00210]).
Thorne discloses the oncolytic viruses can comprise multiple modifications which result in a greater therapeutic effect against tumor cells, as compared to an otherwise identical virus that does not comprise the modifications (paragraph [00174]).
However, Thorne does not disclose wherein the CXCR4 protein comprise a substitution corresponding to Y157 of SEQ ID NO: 20, as required by instant claim 1.
Thorne-2 discloses recombinant oncolytic viruses, including vaccinia viruses, which encodes an exogenous nucleic acid encoding STAT3 modulators, including STAT3 inhibitors, wherein the STAT3 modulator is inserted into the oncolytic viral genome, wherein the recombinant viruses are formulated as pharmaceutical compositions and administered to treat tumors (see, Abstract, paragraphs [0006]-[0007], [0013]-[0020], [0066]-[0069], [0076], [0082], [0140]-[0145], [0182]).
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The UniPro entry P61073 for CXCR4 discloses the human CXCR4 amino acid sequence, which is 100% identical to SEQ ID NO: 20:
Denizot discloses cells expressing CXCR4 mutants comprising the substitution of tyrosine 157 with alanine results in a CXCR4 protein that is able to bind extracellular ligand, but is unable to activate STAT3 signaling (Abstract, FIG 1, page 999-1005).
It would have been obvious to combine the disclosures of Thorne with Thorne-2, Unipro entry P61073 and Denizot. A skilled artisan would have been motivated to substitute the CXCR4 protein of Thorne with a mutated CXCR4 protein comprising a substituted tyrosine 157 because Thorne discloses the CXCR4 proteins can be mutated, and the viruses can encode STAT3 modulators, Thorne-2 discloses STAT3 modulators that inhibit STAT3 signaling can be encoded in an oncolytic virus genome, and the human CXCR4 sequence was known, and the amino acid residue of CXCR4 that results in a CXCR4 protein capable of binding ligand, but unable to activate STAT3 signaling was known in the art (MPEP 2143(I)(A)). A skilled artisan would have had a reasonable expectation of success in practicing the claimed invention, and generating mutations in CXCR4, and encoding CXCR4 proteins in oncolytic viruses was known in the art at the time of the invention.
Claims 2 and 3 are obvious for the same reasons as stated above. Combination of the cited art renders obvious oncolytic viruses encoding CXCR4 proteins comprising the claimed substitutions/sequence.
With regard to claims 4-7, wherein the oncolytic viruses is a poxvirus including vaccinia virus, such as western reserve strains, myoxoma virus, vesicular stomatitis virus, betaentomopoxvirus, a yatapoxvirus, a cervidpoxvirus, etc. (paragraphs [0072], [0080], [0323]).
With regard to claim 8, Thorne discloses the viruses comprise modifications which reduce an immune response targeting a virus-infecting cells and increases an immune response targeting cells surrounding the virus-infected tumor cells (paragraphs [0169]-[0180]).
With regard to claims 9-12, Thorne discloses wherein the oncolytic virus further comprises a mutation or deletion of a viral gene selected from A52R, VH1, A33, K7R, B8R, B15R, KIL, NIL, E3L, and thymidine kinase (TK) a functional domain or a fragment or a variant thereof, or any combinations thereof (paragraphs [0034], [0047]-[0066], [0068], [0220]-[0228], [0315], [0357]).
With regards to claims 13-16, Thorne discloses the oncolytic viruses are used in methods of treating cancer solid cancer or blood cancer (leukemia), and administered via intratumoral or intravenous administration (paragraphs [0077]-[0078], [0094]-[0096]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY A ARON whose telephone number is (571)272-2789. The examiner can normally be reached Monday-Friday 9AM-5PM.
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KAA
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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