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 .
This office action is in response to the paper filed on 3/16/2026. Claims 1-16 were previously presented. Claims 17-20 are newly presented.
Election/Restriction
Applicant’s election of the inventions of Group II (Claims 5-9 and 15-16), drawn to a method for treating a tumor-based disease characterized by expression of a putative Zika virus receptor protein, is acknowledged.
Applicant elects the invention of Group II (Claims 5-9 and 15-16) and the following species: Axl as the putative Zika virus receptor protein and ovarian cancer as the tumor type.
Claims 1-4 and 10-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention and claims 6, 8, 9, 15, and 16 are withdrawn as being drawn to a non-elected species, there being no allow generic or linking claim. Applicant newly add claims 17-20 and provides support for the newly added claims in the specification. Election was made without traverse in the reply filed on 3/16/2026.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Application Status
The action is written in response to applicant’s correspondence received 3/16/2026. Claims 5, 7, and 17-20 are currently pending in the instant application.
Priority
This application claims priority to provisional application 63/407,480, filed on 9/16/2022.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Hyperlinks can be found in the first paragraph under the section ‘DETAILED DESCRIPTION’ and the first paragraph under ‘Transfection and Infection with Zika Virus’. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term LipofectamineTM, MessengerMAXTM, ThermoFisherTM/InvitrogenTM, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Regarding all claims, applicant does not define wherein the AXL-positive tumor is in a subject. The instant specification discloses experiments in vitro (Pg. 16) and in vivo (Pg. 34). Applicant does recite a method “reducing the size of a tumor”, which can be interpreted as a form of treatment, implying the claimed method applies to an in vivo subject.
With regards to claims 5, 7, and 17-20 of the instant application, the claim recites “a method of reducing the size of an Axl-positive tumor, the method comprising infecting the Axl-positive tumor with an oncolytic Zika virus”, an oncolytic Zika virus can refer to any Zika virus. It is disclosed in the specification (on page 15) wherein the Zika virus for administration may comprise naturally occurring or modified, or purified Zika virus or Zika virus RNA or its derivatives.
With regards to claim 5, the claim “a method of reducing the size of an Axl-positive tumor”, the phrase ‘reducing in size’ can be interpreted as a method that has an oncolytic effect on a tumor, as an oncolytic effect is a significant factor of tumor cell death and size. The specification of the instant application merely states “treat” a tumor can refer to reducing the size or extent of a tumor, or reducing the number or sizes of tumor metastases, or slowing down the progression of the tumor (see Pg. 8 of instant specification).
With regards to claim 20, “the volume of an Axl-positive tumor when measured at least 21 days following infection, is less than about 150% of a tumor volume prior to infecting the AXL-positive tumor with the oncolytic Zika virus” refers to where the volume of a post-treatment AXL-positive tumor, after 21 days, exhibits a decrease up to 150%, + or – 5% (about - as defined in the specification), but not exceeding, compared to the volume of the tumor prior to treatment with an oncolytic Zika virus. This establishes a range wherein the decrease in volume can be anywhere from 1% change up to 155% change in tumor size.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 5, 7, and 17-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
With regards to the breath of the claims, the instant claims recite a method of reducing the size of an Axl-positive tumor, the method comprising infecting the Axl-positive tumor with an oncolytic Zika virus, wherein the Axl-positive tumor comprises cells expressing Axl. As defined by the specification of the instant application, a Zika virus can refer to any naturally occurring Zika virus (WT), modified Zika virus or purified Zika virus RNA. Purified Zika virus RNA can be interpreted as Zika virus mRNA, both from naturally occurring and modified Zika viruses, implemented in a vector or any means to express said mRNA in a cell.
With regards to species described by complete structure or reduction to practice, the instant specification discloses four working examples (strains MR766, PRVABC59, and the Nicaragua and Brazil strains), which possess no genetic modifications (see page 17), tested in vivo and in vitro. Applicant does not provide evidence of working examples of any modified Zika viruses, but does provide an example of purified Zika virus MR766 transfected into cultured SkOV3 ovarian cancer cells (see pg. 35 of the instant specification).
With regards to identifying characteristics, the instant specification discloses an oncolytic zika virus as a zika virus which can kill a susceptible cancerous cell by direct lytic infection, induction of apoptosis, induction of autophagy, or by initiating an immune response to viral antigens (see pg.11, line 13). Furthermore, a driving factor of oncolytic zika viruses is cancer cells overexpressing CD24 and/or AXL (see pg. 8, line 20).
State of the prior art shows that oncolytic zika virus, naturally occurring and modified, can have an oncolytic effect on cancer cells in vitro and in vivo, specifically tumor cells associated with the central nervous system (Zhu et al., Zika virus has oncolytic activity against glioblastoma stem cells, Journal of Experimental Medicine, Volume 214, Issue 10, all pages, 10/2/2017). However, prior art infected glioblastoma cells with representative African and American ZIKV strains, not Zika Virus mRNA. It is unclear whether the infection of tumors with purified mRNA would yield a reduction in tumor size.
Taken together, it is clear that the applicant does not have possession of all embodiments of the invention as claimed (any WT, modified, or purified Zika Virus strain or viral RNA) as applicant does not provide evidence for a modified Zika virus nor enough representative species to cover all naturally occurring Zika viruses, modified Zika viruses, or purified Zika virus mRNA.
In view of the foregoing, it is concluded that the instant specification fails to adequately described the claimed method in such a way as to reasonably convey to one skilled in the relevant art that the instant co-inventors had possession of the claimed invention at the time the application was filed.
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 19 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.
Regarding claim 19, claim language recites ‘the method of claim 5, wherein infecting the Axl-positive tumor with an oncolytic Zika virus inhibits growth of the Axl-positive tumor’. This claim is indefinite because applicant already introduces an oncolytic Zika virus in claim 5. Here, examiner is unsure whether the introduced Zika virus of claim 19 is the same Zika virus of claim 5, which claim 19 is dependent on, or a different Zika virus all together.
This rejection can be overcome by defining the oncolytic Zika virus of claim 19 as either ‘the’ oncolytic Zika virus, referring to the same Zika virus of claim 5, or defining what Zika virus is introduced if it is a new virus.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 5, 17, 18, 19, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arumugaswami et al. (US 2019/0192593 A1, published 6/27/2019).
Claim(s) 5, 17, 18, 19, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arumugaswami et al.
Regarding claim 5, Arumugaswami teaches a method for inducing an oncolytic effect on a tumor, comprising administering a composition comprising a Zika virus (ZIKV) to a subject in need thereof to induce the oncolytic effect on the tumor, wherein the tumor expresses a flaviviral cell entry receptor selected from the group wherein AXL is included (see paragraph 0006). Fig 3A-3C of Arumugaswani teaches the oncolytic effect on Glioma cells by administering ZIKV.
Regarding claim 17, Arumugaswami teaches where the tumor expresses flaviviral cell entry receptor AXL at least 1.1 fold to 10 fold higher than non-tumor cells (see paragraph 0055).
Regarding claim 18, Arumugaswami teaches, in various embodiments, the subject in need thereof is a subject who has been diagnosed with a tumor that expresses the flaviviral cell entry receptor AXL (see paragraph 0063).
Regarding claim 19, Arumugaswami teaches wherein the instructions can comprise administering the composition to a subject in need thereof to induce an oncolytic effect on a brain tumor, an ocular tumor, or reintoblastoma (see paragraph 0020). These tumors express a flaviviral cell entry receptor AXL (see paragraph 0020). Fig. 3A-3C show how administering ZIKV induces cell death and cell growth/size in Glioma cells (brain tumor).
Regarding claim 20, Arumugaswami teaches Fig. 3A-C which depicts the oncolytic effect of ZIKV on Glioma cells in accordance with various embodiments of the present invention. Fig. 3A shows glioblastoma cells rounded up and treated with and without ZIKV. In the ZIKV wells, mainly cellular debris was found wherein untreated wells formed tumoroids and filamentous cellular networks (see paragraph 102). Though Arumugaswami does not teach the limitations of 21 days or where the volume of the Axl-positive tumor, when measured at least 21 days following infection, is less than about 150% of a tumor volume prior to infection, Arumugaswami teaches the structural limitations of the tumor (that being a cancer cell that expresses AXL) and the method of administering a virus to achieve an oncolytic effect. The outcome claimed in the instant application is a byproduct that will naturally flow from the method step taught by Arumugaswami.
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.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Arumugaswami et al. (US 2019/0192593 A1, published 6/27/2019) in view of Alexander et al. (US 2019/0038685 A1, published 2/7/2019), in further view of Zwernik et al. (AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines, Molecular Therapy Oncolytics, Volume 23, Pgs. 447-457, 2021), Mazar et al. (Zika virus as an oncolytic treatment of human neuroblastoma cells requires CD24, PLoS One, All pages, 2018), and Martin et al. (Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization, Cell Reports, Volume 13, Issue 11, Pgs. 2456-2469, 2015).
Regarding claim 7, Arumugaswami teaches the method of administering an oncolytic zika virus to see an oncolytic effect (reduction in size) of an Axl-positive tumor, as described above. Furthermore, Arumugaswami teaches where the subject has been diagnosed with a tumor that expresses flaviviral cell entry receptor GRP78, SDC2, TYRO2, AXL, or combinations thereof (see paragraph 0063).
Arumugaswami does not teach wherein the Axl-positive tumor comprises of cells expressing both Axl and CD24.
Regarding claim 7, Alexander teaches a method for treating a CD24 positive tumor in an individual in need of such treatment, the tumor comprising malignant cells charactered by the presence of CD24, the method comprising administering to the subject an effective amount of an oncolytic Zika virus (see paragraph 0021).
Zwernik teaches where cells expressing AXL are permissive for ZIKV infection, while cells that do not express AXL are not (see abstract). Zwernik teaches where survival for patients with glioblastoma is low and where treatments have not evolved and survival has not improved with current cancer therapies (see introduction).
Mazar teaches where permissive Zika virus infection in neuroblastoma cells directly correlates with CD24 expression (see results) and where most neuroblastoma will progress relentlessly despite aggressive chemotherapy, radiation, and even autologous transplantation (see introduction).
Martin teaches where cancer cells can express both CD24(+)AXL(+), and where said cancer cells show a higher lung metastasis competence compared to their more epithelial counterparts (see Fig. 11).
It would have been obvious to one with ordinary skill in the art, before the effective filing date, to combine the methods taught in Arumugaswami and Alexander to target a cell tumor expressing both AXL and CD24.
One would expect a reasonable expectation of success as Arumugaswami teaches that multiple oncogenes can be expressed in a tumor cell, including AXL. Alexander teaches that CD24 is another oncogene expressed in tumor cells and is a target of an oncolytic zika virus.
One would be motivated to combine these methods to target a tumor cell expressing both AXL and CD24 as both Zwernik and Mazar teach where AXL and CD24 positively affect ZIKV ability to infect a cancer cell. Both Zwernik and Mazar also teach that cells that express these oncogenes are typically resistant to current treatment standards. Martin teaches that cancer cells can express both CD24 and AXL at the same time. Therefore, one would be motivated to combine these prior teachings in order to produce a method to effective use Zika viruses to target cancer cells when other known cancer therapies are insufficient.
In view of the foregoing, claim 7 is rejected under 35 U.S.C. 103 as being prima facie obvious before the effective filing date.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 5 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 10993975 B2 in view of Arumugaswami et al. (US 2019/0192593 A1, published 6/27/2019) in view of Alexander et al. (US 2019/0038685 A1, published 2/7/2019), in further view of Zwernik et al. (AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines, Molecular Therapy Oncolytics, Volume 23, Pg. 447-457, 2021), Mazar et al. (Zika virus as an oncolytic treatment of human neuroblastoma cells requires CD24, PLoS One, All pages, 2018), and Martin et al. (Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization, Cell Reports, Volume 13, Issue 11, Pg. 2456-2469, 2015).
As described above, the teachings of these prior arts show that cancer cells expressing AXL or CD24 are suitable targets for oncolytic Zika viruses (both naturally occurring and modified. Furthermore, Martin shows that AXL and CD24 are oncogenes that can be simultaneously expressed within a cancer cells.
Claim 1 of the issued patent recites “a method for reducing the size of a CD24 positive tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of an oncolytic Zika virus, wherein the effective amount is an amount sufficient to reduce the size of the CD24 positive tumor”.
Comparing the claims, both claim a method for reducing the size of a tumor expressing the claimed oncogene (being AXL or CD24). The specification of issued patent and instant application define administration as being administered intravenously (Column 4, line 42 of the issued patent and Pg. 20 of the instant application) and both define a Zika virus as a naturally occurring Zika virus (see claim 7 of the issued patent and Pg. 16 of the instant specification).
It would have been obvious to modify the issued patent to include targeting tumor cells expressing AXL and/or CD24, as it is known in the art that hard to target cancer cells expressing CD24 can also express AXL. Given no modification to the claim language of the instant application, applicant is claiming the same method of administration, as well as the same composition of said method (a naturally occurring Zika virus) in the issued patent. As cancer cells expressing either oncogene are known targets of naturally occurring Zika virus, the claimed method of “reducing size” is patentably indistinct.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID YU whose telephone number is (571)272-1118. The examiner can normally be reached Monday-Friday 7:30 am -5 pm.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635