DETAILED ACTION
This action is in reply to papers filed 10/7/2025. Claims 1, 3-14 and 16-29 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20220241388A1, Published 8/4/2022.
Maintained Rejection(s)
The 103 (a) rejection of claims 1,3-7, 13-14, 18-26 are rejected under 35 U.S.C. 103 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377-385) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011;) is maintained. Applicant’s arguments will addressed following maintained rejection.
The 103 (a) rejection of claims 8-9 and 11-12 as being unpatentable over 1,3-7, 13-14, 18-26 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377-385) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011) and further in view of Irving et al. (PgPub US20100203056A1, Filed 12/8/2009) is maintained. Applicant’s arguments will addressed following maintained rejection.
The 103 (a) rejection of claim 10 as being unpatentable over claims 1,3-7, 13-14, 18-26 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377-385) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011) and further in view of Jin et al. (Hum Gene Ther. 2002 Mar 1;13(4):497-508.) is maintained. Applicant’s arguments will addressed following maintained rejection.
The 103 (a) rejection of claim 17 as being unpatentable over claims 1,3-7, 13-14, 18-26 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377-385) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011) and further in view of Betancourt et al. (PgPub US20140017787A1) is maintained. Applicant’s arguments will addressed following maintained rejection.
The 103 (a) rejection of claim 27 as being unpatentable over claims 1,3-7, 13-14, 18-26 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377-385) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011) and further in view of Antonia et al. (Annals of Oncology 25 (Sep 2014): iv466.) is maintained. Applicant’s arguments will addressed following maintained rejection.
Claims 1, 3-14 and 16-28 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US11285194. Applicant’s arguments will addressed following maintained rejection.
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20220241388A1, Published 8/4/2022.
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.
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.
Prior Art Rejection 1
Claims 1,3-7, 13-14, 18-26 remain and new claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377–385;) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011). Although maintained, the rejection has been update to reflect amendments made to claim 1 and new claim 29.
Regarding claim 1 (in-part) and claim 14 (in-part), Aguilar-Cordova teaches a method of decreasing or retarding an increase in a solid tumor (as in claim 3)(Pg. 6, para. 54) comprising (a) administering, via an injection, an oncolytic (Pg. 5, para. 42) vector (as further in claim 1) comprising an immune stimulating cytotoxic gene (as in claim 4) therapy in conjunction with (b) one or more immune checkpoint modulating agents administered sequentially to an individual for the treatment of a tumour, in a non-human animal or a human (see also Aguilar-Cordova claim 1). Aguilar-Cordova teaches the one or more immune checkpoint modulating agent is selected from monoclonal antibodies with specific affinity for proteins with immune inhibitory activity such as CTLA4, PD1, or PDL1 (Pg. 7, para. 63-65; Pg. 3, para. 22) (as in claim 20, claim 21, claim 22, claim 23, and claim 26). Aguilar-Cordova teaches the oncolytic vector is a vaccinia virus (as further in claim 1 and as further in claim 14) (Pg. 3, para. 24). As evidenced by Chakrabarti et al. (attached herewith) a vaccinia virus is a member of the poxvirus family (as in claim 29) (see Pg. 1094, Col. 1, para. 1). Additionally, Aguilar-Cordova teaches the oncolytic vector is administered in combination with radiotherapy or chemotherapy (as in claim 5) in the cancer patient to further induce a systemic anti-tumour immune response (see also Aguilar-Cordova claim 12; Abstract). Aguilar-Cordova teaches the tumor is a malignant glioma (Pg. 9, para. 80) or a malignant melanoma (Pg. 1, para. 4) (as in claim 24 and claim 25).
However, Aguilar-Cordova fails to teach adipose-derived stromal stem cells (as further in claim 1, claim 13 and claim 14).
Before the effective filed date of the claimed invention, Josiah et al. taught glioblastoma multiforme (GBM) accounts for the majority of primary malignant brain tumors and remains virtually incurable despite extensive surgical resection, radiotherapy, and chemotherapy. Treatment difficulty is due to its exceptional infiltrative nature and proclivity to integrate into normal brain tissue. Long-term survivors are rare, and median survival for patients is about 1 year. Use of adult stem cells as cellular delivery vehicles for anticancer agents is a novel attractive therapeutic strategy. Josiah hypothesized that adipose-derived stem cells (ADSCs) (as further in claim 1 and claim 14 and as in claim 13) possess the ability to home and deliver the oncolytic myxoma virus to glioma cells and experimental gliomas. Josiah infected ADSCs with vMyxgfp and found them to be permissive for myxoma virus replication. ADSCs supported single and multiple rounds of replication leading to productive infection. Further, in vivo orthotopic studies injected with vMyxgfp-ADSCs intracranially away from the tumor demonstrated that myxoma virus was delivered by ADSCs resulting in significant survival increase (Pg. 377, Col. 1; Pg. 281, Col. 2, para. 1). Josiah concludes that their studies form the proof of principle that a cellular carrier like ADSC is effective at delivering myxoma virus at sites distant from the injection site. Josiah adds that this is an important consideration for translation due to the highly infiltrative nature of brain tumors (Pg. 383, Col. 2, para. 3).
However, neither Aguilar-Cordova nor Josiah et al. teach the adipose stromal cells are derived from the stromal vascular fraction (SVF) (as further in claim 1). Further, none of the references teach the adipose stromal stem cells are autologous (as in claim 7 and claim 18) or allogeneic (as in claim 6 and claim 19).
Before the effective filing date of the claimed invention, Takei taught use of adipose tissue-derived mesenchymal stem cells (Pg. 4, para. 10) isolated from the stromal vascular fraction (Pg. 4, para. 15) (as further in claim 1). Takei teaches such cells exert an antitumor effect (Pg. 7, para. 55). Takei teaches to avoid problems of immune rejection, it is preferable that the cells are autologous (Pg. 4, para. 12) (as in claim 7 and claim 18). However, Takei notes that this does not preclude the use of an allogeneic source (as in claim 6 and claim 19).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Aguilar-Cordova, wherein Aguilar-Cordova teaches a method of decreasing or retarding an increase in a solid tumor comprising injecting an oncolytic vector comprising an immune stimulating cytotoxic gene therapy in conjunction with one or more immune checkpoint modulating agents administered sequentially to an individual for the treatment of a tumor with the teachings of Josiah et al., wherein Josiah taught adipose-derived stem cells (ADSCs) possess the ability to home and deliver an oncolytic virus to solid tumors, with a reasonable expectation of arriving at the claimed invention.
A person of skill in the art would have been motivated to modify the method of Aguilar-Cordova such that ADSCs of Josiah carry the oncolytic vector because, as noted by Josiah, a cellular carrier like ADSC is effective at delivering an oncolytic vector at sites distant from the injection site. Additionally, the skilled artisan would have found it prima facie obvious to substitute the ADSCs of Josiah for the SVF derived ADSCs of Takei because Takei teaches their ADSCs possessed anti-tumor effects.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Applicant’s Arguments/Response To Arguments
Applicant argues: The AdV-tk vector delivers the gene encoding the enzyme Herpes simplex virus thymidine kinase (HSV-tk), which activates the prodrug. AdV-tk, is a "gene delivery vehicle" as described by Aguilar-Cordova. The AdV-tk vector it is not an oncolytic vector, as alleged by the Examiner. The AdV-tk vector is administered intratumorally where it delivers a gene encoding an enzyme that activates a systemically (e.g., orally) administered prodrug. The
prodrug is inactive except in the presence of the enzyme, which is delivered into the tumor. Once the prodrug is activated in the tumor microenvironment by the AdV-tk encoded enzyme, the prodrug kills tumor cells. The AdV-tk vector does not lyse or kill tumor cells, the activated prodrug does.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Per MPEP 2123 (I), ““The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).” Examiner does not dispute that the Examples of Aguilar Cordova are drawn towards the use of adenoviral vectors; however, as widely known, a patent or patent application is prior art for all that it teaches.
Applicant argues: It is well-known in the art that AdV-tk, also known as aglatimagene besadenovec, is a replicating viral vector, and that a non-replicating virus is not and cannot be a lytic or oncolytic virus or vector since a lytic virus must replicate. For example, Li et al. (2007), Clin. Cancer. Res. 13(19):5847-5854, published before the earliest priority date for the instant
application, states that "the replication-deficient adenovirus mutant ADV-TK is a chimeric
human group C adenovirus (ADV5) that expresses HSV-TK" (see, e.g., page 5849, left
column, 3rd paragraph of Li et al. (2007)). Thus, it had been known that AdV-tk is a nonreplicating virus that functions to deliver a genetic cargo (HSV-tk). The "genetic cargo"
activates a separately administered agent (the prodrug), that, upon activation by the delivered
HSV-tk, destroys tumor cells. AdV-tk itself, thus, does not kill or lyse tumor cells. It is not a
lytic virus or "oncolytic vector." The Examiner states that Aguilar-Cordova teaches the use of an "oncolytic vector" comprising an "immune stimulating cytotoxic gene therapy," and that the "oncolytic vector" is a vaccinia virus and refers to paragraph [0024] of Aguilar-Cordova (Examiner’s emphasis). This is not correct. The adenovirus vector of Aguilar-Cordova is not an oncolytic vector, and it is not administered in a cell of any kind. There is no mention an "oncolytic vector" in Aguilar-Cordova other than in describing allegedly inferior prior art methods (involving oncolytic virus therapy) and distinguishing oncolytic therapy from its methods. Paragraph [0024] of Aguilar-Cordova does not teach or suggest the use of an oncolytic virus, nor does it teach or suggest the combination of an oncolytic virus with a treatment that activates a T cell response, nor providing the virus in an adipose stromal stem cells or an SVF containing the cells. Paragraph [0024] certainly does not teach, suggest, or even hint at, the use of a vaccinia virus, an oncolytic virus, nor the combination of such oncolytic viral therapy with an immune therapy, nor delivery of a vaccinia virus in adipose stromal cells or an SVF that comprises such cells.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. As noted above, and as copied below, the Examiner did not cite para. 24. Rather, Examiner cited para. 42. Para. 42 is also copied below.
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Note that para. 42 clearly teaches that an oncolytic virus may be administered to a subject having cancer in an amount sufficient to exert oncolytic activity, causing attenuation or inhibition of tumor cell proliferation leading. Para. 24 teaches examples of oncolytic viruses, and viruses from which oncolytic virus have been derived include … vaccinia virus.
Applicant argues: The adenoviral vector taught by Aguilar-Cordova does not deliver a cytotoxic agent; it delivers a gene encoding an enzyme that converts a prodrug into a cytotoxic agent. The anti-tumor agent is generated at the tumor site, from the action of the enzyme on the prodrug. If the proposed modification or combination of the prior art would change the
principle of operation of the prior art invention being modified, then the teachings of the
references are not sufficient to render the claims prima facie obvious. In re Ratti, 270 F.2d 810, 123 USPQ 349 (CCPA 1959). The instantly claimed methods require an adipose stromal cell or SVF containing a vaccinia virus, and do not require the activation of a systemically administered prodrug to kill tumor cells. The methods of Aguilar-Cordova encode an enzyme that activates a prodrug.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. In response to arguments regarding the pro-drug of Aguilar-Cordova, it must be noted that the claim recites the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. Should Applicant wish to exclude elements from Aguilar-Cordova, Applicant should consider substituting the term “comprising” for “consisting” which excludes any element, step, or ingredient not specified in the claim.
Applicant argues: Josiah et al., thus, provides no teachings or suggestions for using another virus besides myxoma virus, such as a vaccinia virus, which, as known by one of ordinary skill in the art, has very different tropism. Vaccinia virus infects and causes disease in humans, and many humans have acquired immunity against vaccinia virus. These properties are the opposite of the reasoning in Josiah et al. for selecting myxoma virus. person of ordinary skill in the art would not have modified the methods of Josiah et al. by infecting ADSCs with vaccinia virus, because Josiah et al. specifically teaches that the use of ADSCs as carriers overcomes limitations that are specific to myxoma virus anti-tumor efficacy, particularly its inability to infect and replicate in human cells or to infiltrate the human brain and migrate to brain tumors. Vaccinia virus is not limited in its ability to infect and replicate in human cells and tumors. Thus, there is no teaching or suggestion in Josiah et al., nor any reason, that would have led one of ordinary skill in the art to have modified the methods of Josiah et al. to use vaccinia virus instead of myxoma virus (nor the methods of Aguilar-Cordova, which do not use any oncolytic virus).
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. This is because the Examiner did not cite Josiah et al. for “for replacing its myxoma virus with a vaccinia virus.” As noted in paragraph 17 of instant office action (and as previously recited), a person of skill in the art would have been motivated to modify the method of Aguilar-Cordova such that the ADSCs of Josiah carry the vaccinia virus of Aguilar Cordova because, as noted by Josiah, a cellular carrier like ADSC is effective at delivering an oncolytic vector at sites distant from the injection site. The Examiner did not suggest replacing the myxoma virus taught by Josiah et al. with the vaccinia virus taught by Aguilar-Cordova.
Applicant’s argument that “Josiah et al. specifically teaches that the use of ADSCs as carriers overcomes limitations that are specific to myxoma virus anti-tumor
Efficacy” is belied by the title of Josiah- “Adipose-derived Stem Cells as Therapeutic Delivery Vehicles of an Oncolytic Virus for Glioblastoma.” Note the use of the generic ‘oncolytic virus’ in the title. Additionally, in the abstract, Josiah teaches “Our data suggest that ADSCs are promising new carriers of oncolytic viruses, specifically myxoma virus, to brain tumors.” (Examiner’s emphasis). There is nothing in Josiah that would dissuade one of ordinary in the skill in the art from using ADSCs to deliver oncolytic viruses that are not myxoma viruses. The Courts have consistently held that “”Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).”
Applicant argues: The instant pending claims require that the cells contain a lytic vaccinia virus; it is the cells comprising the virus that are the therapeutic agent. In Takei et al. , the stem cells are a monotherapeutic agent for treating prostate cancer. Takei et al. teaches that ASCs suppress the growth of prostate cancer cells via direct cell-to-cell interaction, and that the hum oral component secreted by ASCs has no anti-tumor effect (see, e.g. , paras. [0006] and [0046][ 0049]). Takei et al. teaches that it is preferable to administer the ASCs by local injection into the prostate cancer lesion, or around it, or into a metastatic site or around it (see, e.g., para. [0033] and claim 9). Thus, the stem cells are not required "to migrate" to the tumor cells, as taught by Josiah et al.
In Response: As previously noted, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). The combination of Aguilar-Cordova, Josiah et al. and Takei et al. teach the claimed invention.
Applicant argues: Josiah et al. does not teach or suggest the use of ADSCs
or any stem cells for the treatment of gliomas or any tumors. Josiah et al. teaches that ADSCs
do not contribute to the growth of tumors, but also do not possess any anti-tumor effects
against gliomas. The ordinarily skilled person would not seek to use isolated ADSCs, derived
from SVF or otherwise, nor any other type of stem cells, alone (without virus) for the
treatment of tumors, since Josiah et al. shows that ADSCs do not exert any anti-tumor
effects. Additionally, there is no indication, in Josiah et al. or Takei et al., that the specific
method for isolating the adipose-derived stem cells would affect their anti-tumor effects.
There is no teaching or suggestion that ADSCs, isolated from SVF by the methods of Takei
et al., would behave any differently against gliomas than ADSCs isolated "via lipo-aspiration
from healthy female donors," as described in the methods of Josiah et al., in the 2nd column
on the bottom of page 383, in the section entitled "Cell lines." There is no reason why one of
ordinary skill in the art would have arrived at such a conclusion, particularly when Josiah et
al. definitively shows that the isolated ADSCs alone do not exert anti-tumor effects against
gliomas, and when Takei et al. teaches that isolated ASCs only exert anti-tumor effects
against prostate cancer
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. This is because it is unclear what Applicant is arguing as the cells would not be empty; but , rather would comprise the vaccinia virus of Aguilar-Cordova.
Applicant argues: The combination of the teachings of Aguilar-Cordova, Josiah et al. and Takei et al. does not teach or suggest methods for treating cancer, comprising injecting into a subject an SVF composition containing stem cells, or adipose-derived stromal stem cells that contain a vaccinia virus, and then administering a treatment that activates a T-cell response. For the reasons discussed above, the combination of the teachings of Aguilar-Cordova, Josiah et al.,
and Takei et al. does not teach or suggest the claimed methods, and none of the cited
references suggests replacing the non-replicating, non-lytic gene delivery adenoviral vector of Aguilar-Cordova with a lytic virus, nor delivering the gene delivery vector in a cell. None of Aguilar-Cordova, Josiah et al. and Takei et al. , singly or in combination, suggests treatment with an immune checkpoint inhibitor, following the administration of the lytic virus and adipose derived stem cells or SVF containing adipose derived stem cells, which enhances an anti-tumor immune response.
In Response: As previously noted, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). The combination of Aguilar-Cordova, Josiah et al. and Takei et al. teach the claimed invention.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Prior Art Rejection 2
Claims 8-9 and 11-12 remain rejected under 35 U.S.C. 103 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377–385) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011) as applied to claims 1,3-7, 13-14, 18-26 and 29 above, and further in view of Irving et al. (PgPub US20100203056A1, Filed 12/8/2009).
Aguilar-Cordova et al., Josiah et al. and Takei et al. teaches administering a treatment to the subject that activates a T-cell response within the subject, however none of these references teach promoting simultaneous signaling through the T cell receptor and a costimulatory molecule (as in claim 8 and claim 16), such as CD28 (as in claim 9) or administering agonistic antibodies directed against activating co-stimulatory molecules (as in claim 11), wherein the agonistic antibodies are selected from among CD28 (as in claim 12). Moreover, none of the aforementioned references teach step (b) comprises administering an anti-CTLA-4 antibody or an anti-PD-L1 antibody, or an anti-PD-1 antibody (as in claim 28).
Irving teaches CD28 interreacts with B7.1 and B7.2 to transmit a signal that synergizes with the TCR signal to promote T-cell activation. Irving teaches CD28 activation sustains T-cell responses by promoting T-cell survival thereby enabling cytokines to initiate T-cell clonal expansion and differentiation (Pg. 8, para. 73). Irving also teaches CTLA-4 plays an important role in regulating T-cell responses, including peripheral T-cell tolerance. While it is not clear how signaling is coordinated through CTLA-4 and CD28, some possibilities include out-competing CD28 for binding to B7, by induction of immunosuppressive cytokines, direct antagonism of CD28 signaling and/or TCR-mediated signaling. As a result, Irving notes that the antagonism of CTLA-4 (e.g., antagonist anti-CTLA antibodies (as in claim 28)) and or agonizing B7.1/B7.2/CD28 may be useful to enhance immune response in the treatment of infection (e.g., acute and chronic) and tumor immunity (as in claim 8, claim 9, claim 11, claim 12 and claim 16) (Pg. 9, para. 75).
When taken with the teachings of Aguilar-Cordova et al., Josiah et al. and Takei et al., one of ordinary skill in the art would have found it prima facie obvious to promote simultaneous signaling through the T cell receptor and a costimulatory molecule because Irving teaches such may be useful to enhance immune response in tumor immunity. Thus, in the method of treating a solid tumor, as set forth in the combination of Aguilar-Cordova et al., Josiah et al. and Takei et al., it would have been prima facie obvious.
Applicant’s Arguments/Response To Arguments
Applicant argues: Irving does not teach or suggest adipose-derived stromal stem cells or SVF containing stem cells, nor their use as carrier of any lytic virus, nor the administration of adipose-derived stromal stem cells or SVF containing stem cells containing lytic virus. Irving recognizes a merit of promoting simultaneous signaling through the T cell receptor and a costimulatory molecule and teaches the combination of anti-PD-LI antibodies and agonists of activating costimulatory molecules. Irving does not suggest the combination of a lytic virus with a treatment that activates a T cell response within a subject. A search for the terms "lytic virus" or "oncolytic virus" or "vaccinia" revealed zero hits in Irving. Irving cannot suggest the step of administering a treatment to the subject that activates a T-cell response within the subject following the step of injecting into the subject a composition comprising adipose-derived stromal stem cells or SVF containing stem cells, wherein the stem cells contain a lytic virus that kills tumor cells.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. This is because Irving et al. was not cited for teaching a “lytic virus" or "oncolytic virus" or "vaccinia" virus. Rather, Irving was cited for teaching anti-CTLA antibodies and or agonizing B7.1/B7.2/CD28 is useful to enhance immune response in the treatment of infection (e.g., acute and chronic) and tumor immunity.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Prior Art Rejection 3
Claim 10 remains rejected under 35 U.S.C. 103 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014; REF. BA in IDS filed 5/31/22) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377–385; REF. DF in IDS filed 5/31/22) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011; REF. BN in IDS filed 5/31/22) as applied to claims 1,3-7, 13-14, 18-26 and 29 above, and further in view of Jin et al. (Hum Gene Ther. 2002 Mar 1;13(4):497-508.)
The teachings of Aguilar-Cordova et al., Josiah et al. and Takei et al. are relied upon as detailed above. However, none of these references teach step (b) comprises administering to the tumor T-cells that express a growth factor (as in claim 10).
Before the effective filing date of the claimed invention, Jin et al. teach
solid tumor growth can be inhibited by targeting its neovasculature with vascular endothelial growth factor (VEGF)-toxin fusion proteins (FPs), but these agents have been limited by their inability to localize at the tumor site. In this study, Jin and colleagues devised a gene therapy approach intended to deliver VEGF-toxin directly to tumor. Antigen-specific cytotoxic T lymphocytes (CTLs) served as vehicles to deliver a retroviral VEGF-toxin fusion protein (as in claim 10) to its specific leukemia cell target in vivo. VEGF was chosen on the basis of the expression of VEGF receptor on endothelial cells in the tumor neovasculature. In vitro, supernatants collected from transfected cells specifically inhibited the growth of VEGF receptor-expressing human umbilical vein endothelial cells (HUVECs), but not a control cell line. In vivo findings correlated with in vitro findings. A retroviral vector containing the target gene and a nerve growth factor receptor (NGFR) reporter gene was used to transiently transduce T15, a CD8+ CTL line that specifically recognizes C1498, a lethal C57BL/6 myeloid tumor. Transduced T15 cells injected intravenously significantly inhibited the growth of subcutaneous tumor, whereas non-transduced controls did not. Together, these data indicate that gene therapy of T cells with retrovirus containing a VEGF-immunotoxin target gene may be a valid means of inhibiting a broad range of solid tumors dependent on angiogenesis (Abstract; Pg. 500, Col. 2, para. 3+; Pg. 502, Fig. 3).
When taken with the teachings of Aguilar-Cordova et al., Josiah et al. and Takei et al., one of ordinary skill in the art would have found it prima facie obvious to include a treatment of administering T cells expressing a growth factor to a solid tumor because Jin teaches gene therapy of T cells with retrovirus containing a VEGF-immunotoxin target gene may be a valid means of inhibiting a broad range of solid tumors dependent on angiogenesis.
Thus, the combination would have been prima facie obvious.
Applicant’s Arguments/Response To Arguments
Applicant argues: The purpose of the virus in Jin et al. is to express the VEGF-toxin fusion protein. Jin et al. teaches that there is a correlation between the in vitro and in vivo findings. Jin et al. teaches that Tl 5 T cells can systemically deliver the retroviral gene therapy to subcutaneous Cl498 target cells in vivo (e.g., pg. 503, col. 1). Compared to mice receiving a PBS vehicle or non-transduced T cells, T cells carrying the retroviral gene therapy significantly reduced the volume of the subcutaneous Cl498 tumors (e.g., pg. 505, figure 7). There is no teaching or suggestion in Jin et al. of a lytic virus or the use of a lytic virus, such as vaccinia virus. Jin et al. is focused on the delivery of the VEGF toxin fusion protein as a gene therapy.
In Response: As previously noted, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Note that Jin et al. was not cited for teaching a lytic virus or the use of a lytic virus, such as vaccinia virus. This was taught in Aguilar-Cordova. Jin, however, does teach administering T cells expressing a growth factor to a solid tumor because Jin teaches gene therapy of T cells with retrovirus containing a VEGF-immunotoxin target gene may be a valid means of inhibiting a broad range of solid tumors dependent on angiogenesis.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Prior Art Rejection 4
Claim 17 remains rejected under 35 U.S.C. 103 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377–385) and further in view Takei et al. (WO2011070974A1, Published 6/16/2011) as applied to claims 1,3-7, 13-14, 18-26 and 29 above, and further in view of Betancourt et al. (PgPub US20140017787A1).
The teachings of Aguilar-Cordova, Josiah et al. and Takei et al. are relied upon as detailed above. However, none of Aguilar-Cordova, Josiah et al. and Takei et al. teach treating the adipose stromal stem cells with lipopolysaccharide prior to step (a) (as in claim17).
Before the effective filing date of the claimed invention, Betancourt et al. taught an isolated mesenchymal stem cell for use in treating ovarian cancer, wherein said isolated mesenchymal stem cell is incubated with at least one TLR 4 ligand, such as lipopolysaccharide (LPS) (as in claim 17), wherein said incubation reduces tumor growth in the ovarian cancer (see Betancourt claims 32-34).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Aguilar-Cordova et al., Josiah et al. and Takei et al. wherein the combination teaches a method of decreasing or retarding an increase in a solid tumor comprising injecting adipose-derived stem cells comprising an oncolytic vector comprising an immune stimulating cytotoxic gene therapy in conjunction with one or more immune checkpoint modulating agents administered sequentially to an individual for the treatment of a tumor, with the teachings of Betancourt et al., wherein Betancourt teaches incubating stem cells with lipopolysaccharide (LPS) prior to its use in a method for reducing tumor growth, with a reasonable expectation of success.
Examiner notes that the courts held in In re Kerkhoven, 205 USPQ 1069 (C.C.P.A. 1980) held that "it is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose;" wherein the "idea of combining them flows logically from their having been individually taught in prior art." In this regard the combination of Aguilar-Cordova. Josiah et al. and Takei et al. and the teachings of Betancourt are all directed to compositions that reduce tumor growth, thus the combination is prima facie obvious.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Applicant’s Arguments/Response To Arguments
Applicant argues: Betancourt does not teach or suggest the use of adipose-derived stromal stem cells. For example, in paragraph [0044] nor their combination with vaccinia virus. Betancourt does not suggest delivering vaccinia virus in MSCs. In paragraph [0059], Betancourt states that MSCs are "readily separated from other bone marrow-derived cells" and that "MSCs are very attractive candidates/or stem-cell based tissue repair and gene therapy strategies." There is no mention of use for delivering vaccinia virus for any purpose. Betancourt distinguishes human MSCs (hMSCs), which are derived from bone marrow, from human adipose-derived stem cells (hADSCs). For example, in paragraphs [0061] and [00115], Betancourt compares the differing effects of TLR activation on hADSCs, murine MSCs (muMSCs) and hMSCs. By comparing bone marrow-derived MSCs to ADSCs, and describing differences in the effects of TLR activation on MSCs and ADS Cs, Betancourt teaches that the two types of
stem cells are not interchangeable. Betancourt does not teach or suggest that TLR4 priming of ADSCs results in a pro-inflammatory phenotype, nor that LPS-primed ADSCs exhibit anti-tumor effects.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In this regard, the teachings of Betancourt suggest incubating (a first type of human adult) stem cells with lipopolysaccharide (LPS) prior to its use would have the same effect as incubating (a second type of human adult) stem cells with lipopolysaccharide (LPS). Nevertheless, Betancourt at paragraph 60 teaches a connection between the stimulation of specific Toll-like receptors (TLRs) and the immune modulating responses of human multipotent mesenchymal stromal cells (hMSCs) was shown by the following references, which are incorporated by reference in their entireties: Hwa Cho H et al. (2006) Role of toll-like receptors on human adipose-derived stromal cells. (Examiner’s emphasis) In the abstract of Hwa et al. (attached herewith), Hwa teaches “Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and flow cytometry analysis demonstrated that MSCs derived from human adipose tissue and bone marrow express TLR‐1, TLR‐2, TLR‐3, TLR‐4, TLR‐5, TLR‐6, and TLR‐9.” In fact, Hwa actually treated ADSCs with LPS. This establishes a reasonable expectation that the ADSCs can be treated with lipopolysaccharide prior to step (a), as claimed. Motivation to modify ADSCs with LPS is established in Betancourt’s teaching that LPS treated MSCs reduced tumor growth. Expectation of success is found in Hwa’s teaching that demonstrated that MSCs derived from human adipose tissue and bone marrow express TLRs including TLR-4, a receptor that recognizes LPS.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Prior Art Rejection 5
Claim 27 remains rejected under 35 U.S.C. 103 as being unpatentable over Aguilar-Cordova (PgPub US20150086541A1, Effective Filing Date 9/19/2014) in view of Josiah et al. (Mol Ther. 2010 Feb; 18(2): 377–385., previously cited) and Takei et al. (WO2011070974A1, Published 6/16/2011) as applied to claims 1-7, 13-15, 18-26 and 29 above, and further in view of Antonia et al. (Annals of Oncology 25 (Sep 2014): iv466.).
The teachings of Aguilar-Cordova, Josiah et al. and Takei et al. are relied upon as detailed above. And although Aguilar-Cordova teaches the blocking antibody is an inhibitor of the PD-1 pathway, none of Aguilar-Cordova, Josiah et al. and Takei et al. teach the inhibitor of the PD-1 pathway is AMP-244, MEDI-4736, MPDL3280A, or MIHl (as in claim 27).
Before the effective filing date of the claimed invention, Antonio et al. evaluated the safety and efficacy of MEDI4736 (as in claim 27) in patients (pts) with multiple solid tumor types including non-small cell lung cancer (NSCLC). Antonio teaches of the 101 pts treated at the 10 mg/kg q2w dose, all were PS 0–1, with a median of 2.5 prior treatments. In this group, treatment-related adverse events (AEs) were reported in 20% of pts; most frequently dyspnea (16%), fatigue (15%) and nausea (15%). Grade ≥ 3 treatment-related AEs were reported in 4 pts. AEs led to study discontinuation in 6 pts, none of which were treatment-related. Pneumonitis (grade 2) occurred in 1 pt. With a median follow up of 10 wks, 46 pts were followed ≥ 12 wks. Objective response + stable disease was observed in 18 pts to date. While some responses or stabilization were reported at first assessment (6 wks), others appeared following initial progression. Benefit was durable; 72/114 pts remain on study (including 4 pts >52 wks) at data cutoff (see Entire Abstract).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Aguilar-Cordova et al., Josiah et al. and Takei et al. wherein the combination teaches a method of decreasing or retarding an increase in a solid tumor comprising injecting adipose-derived stem cells comprising an oncolytic vector comprising an immune stimulating cytotoxic gene therapy in conjunction with one or more immune checkpoint modulating agents administered sequentially to an individual for the treatment of a tumor, with the teachings of Antonio et al., wherein Antonio evaluated the safety and efficacy of MEDI4736 patients with multiple solid tumor types and found a benefit in 72/114 patients.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Applicant’s Arguments/Response To Arguments
Applicant argues: Antonia et al. teaches the administration and a benefit of administering MEDI4736 to human subjects with cancer. This says little about the instantly claimed methods of treating cancer. Claim 27 depends indirectly upon independent claim 14, which is directed to methods of treating a cancer in a subject, comprising: (a) injecting into the subject a composition comprising adipose-derived stromal stem cells that comprise vaccinia virus; and then (b) administering a treatment to the subject that activates a T-cell response within the subject, where step (a) is performed before step (b). There is no teaching or suggestion of a composition comprising adipose-derived stromal stem cells that contain vaccinia virus in Antonia et al. There is no suggestion of administering MEDI4736 following the administration of the adipose-derived stromal stem cell containing
In Response: : Applicant’s arguments have been fully considered, but are not found persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In this regard, the teachings of Antonio et al. were cited as Antonio evaluated the safety and efficacy of MEDI4736 as a tumor inhibitor against solid tumors.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
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 1,3-14, and 16-28 remain and new claim 29 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US11285194. Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons advanced in the previous office action.
Applicant’s Arguments/Response To Arguments
Applicant argues: Each of instant claims 9, 11, and 12 is directed to particular species of claim 1 of the instant application, the species are not recited in the issued patent; additionally, the claims do not recite species of a claim of the issued patent. They are not "blocking antibody against a negative co-stimulatory molecule" as recited in claim 1 of the patent.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. As previously noted, the difference between the application claims and the patent claims lies in the fact that the patent claim includes many more elements and is thus much more specific. For example, patent claims limit the cancer to a solid tumor or hematologic malignancy. Thus the invention of claims of the patent is in effect a “species” of the “generic” invention of the application claims. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). Since application claims is anticipated by claims of the patent, it is not patentably distinct from claim s of the patent.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Objections and Rejections Necessitated by New Claim 29
Claim Objections
Claim 29 is objected to because of the following informalities: Claim 1 has been amended to limit the lytic virus to a vaccinia virus. Claim 29 recites the lytic virus is a poxvirus. Insofar as the lytic virus has been limited to a vaccinia virus in claim 1, claim 29 should recite the vaccinia virus is a poxvirus.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1 has been amended to limit the lytic virus to a vaccinia virus. Claim 29 recites the lytic virus is a poxvirus. Chakrabarti et al. ( Biotechniques. 1997 Dec;23(6):1094-7., attached herewith) teaches the vaccinia virus is a member of the poxvirus family, has been developed as a vector for the expression of genes in mammalian cells (Pg. 1094, Col. 1, para. 1). Accordingly, claim 29 fails to further limit the limitations of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Appropriate correction is requested.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is 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 extension fee 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 date of this final action.
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/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632