DETAILED ACTION
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 an amendment filed 10/14/2025.
Claims 1-54 are pending.
This application is a continuation of U.S. Patent Application 16/536,073, filed Aug. 08, 2019, now U.S. Patent 11,505,782, which is a continuation of International Application No. PCT/US2019/035464, filed June 04, 2019, which claims the benefit of priority to U.S. Provisional Application 62/680,570, filed June 04, 2018.
Election/Restrictions
Applicant's election without traverse of Group I (claims 1-45) in the reply filed on 10/14/2024 is acknowledged. As well, applicants have elected A) stem cells as a species of carrier cell, B) vaccinia virus that is IHD-W and C) pre-treatment or sensitization that is enhanced immune suppression/evasion by pre-treatment or treatment to load the cell with an IFNg blocker such as VV B8R and D) the iPSC is unresponsive to an IFN induced antiviral state wherein IFNg receptor expression is suppressed. Therefore claims 1-4, 6-8, 16-18, 21, 30, 31 and 33-35 are under examination.
Claims 5, 9-15, 19, 20, 22-29, 32 and 36-54 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Information Disclosure Statement
Information disclosure statements filed 10/14/2025, 11/7/2024, 1/24/2024, 7/18/2023, 4/20/2023 and 11/10/2022 have been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action. Initials indicate that the document has been considered even if the reference is lined through.
Claim Objections
Claims 6, 8 and 17 are objected to because of the following informalities: claim 6 as well as claim 8 require articles prior to each of the cell types. Similarly, claim 17 requires articles prior to each individual viral strain Appropriate correction is required.
Claim Rejections - 35 USC § 112, second paragraph
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 33 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 33 is vague and indefinite in that the metes and bounds of the term “derived from” are unclear. It is unclear the nature and number of steps required to obtained a “derivative” of stem cells. The term implies a number of different steps that may or may not result in a change in the functional characteristics of the factors from the source that it is “derived from”.
Claim Rejections - 35 USC § 112, first paragraph
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.
Claims 1-4, 6-8, 16-18, 21, 30, 31 and 33-35 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a carrier cell comprising an oncolytic virus. The cell has several characteristics that are required. First, the virus can replicate in the cell. Second, the cell can be administered to a human subject and 3) the cell has been treated or modified or both a) to enhance the immunosuppressive properties or immunoprivileged properties of the cell fort administration to a human subject and b) (in claim 1 optionally but in claim 2, 3, 18 required) enhance the amplification of the virus in the cell. Claim 3 adds to this with required treatments or modifications that include one or more of the enhanced amplification of the virus, c) blocking of the induction of an anti-viral state d) immune suppression or immune evasion e) protection against allogeneic inactivation/rejection determinants and e) protection against complement or inhibition of complement activation. Claim 18 repeats some of these properties by requiring enhanced virus amplification as well as blocking of induction of an antiviral states. Claim 21 expands on the block of induction of an anti-viral state of claim 18 by listing a number of potential mechanisms including one or more small molecule or protein inhibitors that interfere with IFN Type I/Type II receptors, interfere with downstream signaling, interfere with IFNAR1/IFNAR2 signaling, interfere with IFNGR1/IFNGR2 signaling, interfere with STAT1/2 signaling, interfere with Jak1 signaling, interfere with Jak2 signaling, interfere with IRF3 signaling, interfere with IRF7 signaling, interfere with IRF9 signaling, interfere with TYK2 signaling, interfere with TBK1 signaling, or interfere with other signaling pathways that effect an immune response against the oncolytic virus in the cell or subject. Claim 30 limits the modification to enhancement of immune suppression./immune evasion with immunosuppressing factors of viral origin and claim 31 these are from among one or more of an inhibitor of immune FAS/TNF/granzyme B- induced apoptosis; an IL-1/NFxB/IRF3 antagonist; an IL-1 and toll-like receptor (TLR) antagonist; an IL-13 antagonist; a TNFa blocker; an IFNa/b blocker; and an IFNg blocker. Claim 33 recites that the cell is engineered to prevent or be unresponsive to IFN induced antiviral states and in claim 34 and 35 these are to be mediated by suppression of one or more of Type I/Type II interferon receptor expression, IFN a/b receptor expression, IFNg receptor expression, IFNAR1/IFNAR2 expression, IFNGR1/IFNGR2 expression, STAT1/2 receptor expression, Jakl/2 receptor expression, IRF3 receptor expression, IRF7 receptor expression, IRF9 receptor expression, TYK2 kinase expression, and TBK1 kinase expression. These are all functional outcomes desired of the cell without structural details. It is noted that claim 4 recites that for amplification of the virus, the cell is pretreated or loaded with growth factor and/or cytokines. But, the growth factors and cytokines are not provided.
What is missing is the structures or molecules that mediate these functions. By claiming the modifiers or treatments of the cells in terms of outcomes, the claims are distinctly drawn to a genus of molecules to mediate these effects. The number of embodiments disclosed in the specification must be commensurate with the magnitude of the claimed genus, particularly if the genus is to cover species that are not known in the prior art. Here, the specification describes a single species that mediates the effect. But, the claims recite the construct in generic terms.
The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is needed. Since the disclosure fails to describe common attributes or characteristics that identify members of the genera, and because the genera are highly variant. The disclosure teaches use of adipose stem cells with vaccinia virus. As to carrier cells that can be administered to a human subject and the virus (vaccinia) can replicate, applicants demonstrate that allogeneic adipose stem cells with HLA matches and modifications to reduce anti-stem cell cytotoxicity and interferon response are required (see example 5).
To accomplish blockage of IFN, 50 mM Ruxolitinib was shown to support virus infection and amplification.
To improve amplification and viral spread, complement blockade was effected by 20 mM Compstatin or 50 ng/ml neutralizing anti-human C3a/C3A antibody.
To suppress the immune response to the carrier cells, anti-HLA blocking antibodies were used.
To evade allogeneic recognition, anti-NKG2D An was used.
Pretreatment of the cells with IL-10 lead to immunosuppression.
Applicants extrapolate these findings to all the functional properties noted above. These are not sufficient to describe the entire genus of any stem cell that can support the replication of vaccinia wherein the cell is modified or treated a) to enhance the immunosuppressive properties or immunoprivileged properties of the cell for administration to a human subject and b) enhance the amplification of the virus in the cell, block of the induction of an anti-viral state, immune suppression or immune evasion, protection against allogeneic inactivation/rejection determinants and e) protection against complement or inhibition of complement activation.
The disclosure of anti-HLA and anti-IFN does not provide adequate mechanisms that support the conclusion that any means to interfere with IFN Type I/Type II receptors, interfere with downstream signaling, interfere with IFNAR1/IFNAR2 signaling, interfere with IFNGR1/IFNGR2 signaling, interfere with STAT1/2 signaling, interfere with Jak1 signaling, interfere with Jak2 signaling, interfere with IRF3 signaling, interfere with IRF7 signaling, interfere with IRF9 signaling, interfere with TYK2 signaling, interfere with TBK1 signaling, or interfere with other signaling pathways that effect an immune response against the oncolytic virus in the cell or subject. There is no demonstration that single demonstrations provide the mechanism for the genus. This is true as well when considering the modification to enhancement of immune suppression./immune evasion with immunosuppressing factors of viral origin wherein there is no indication that an inhibitor of immune FAS/TNF/granzyme B- induced apoptosis; an IL-1/NFxB/IRF3 antagonist; an IL-1 and toll-like receptor (TLR) antagonist; an IL-13 antagonist; a TNFa blocker; an IFNa/b blocker; and an IFNg blocker. Claim 33 recites that the cell is engineered to prevent or be unresponsive to IFN induced antiviral states and in claim 34 and 35 these are to be mediated by suppression of one or more of Type I/Type II interferon receptor expression, IFN a/b receptor expression, IFNg receptor expression, IFNAR1/IFNAR2 expression, IFNGR1/IFNGR2 expression, STAT1/2 receptor expression, Jakl/2 receptor expression, IRF3 receptor expression, IRF7 receptor expression, IRF9 receptor expression, TYK2 kinase expression, and TBK1 kinase expression will lead to the desired cell modification effects.
To this end, the MPEP provides such guidance (emphasis added). If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Compare Fonar, 107 F.3d at 1549, 41 USPQ2d at 1805 (disclosure of software function adequate in that art).
Claim Rejections - 35 USC § 102
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 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.
Claims 1, 6-8, 16 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Szalay and Minev (U.S. 20170043010).
Szalay and Minev teach development of stem cells as vehicles (carriers) of vaccinia virus for cancer therapy (see abstract and ¶0006). The cell is modified to avoid clearance from the immune system (see ¶0044). This meets the requirement that the cell (ImmStem) is modified or treated to reduce immunogenicity and thus enhance the immunosuppressive properties (see ¶0049).
As recited in claim 6-8, the stem cell is selected from a number of stem cells such as mesenchymal (see ¶0005).
The oncolytic virus is for example Western Reserve VV (see e.g. ¶0006) as recited in claims 16 and 17.
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 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.
Claims 1-4, 6-8, 16-18, 21, 30, 31 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Falb et al (U.S. 20190160115) in view of Bell et al (U.S. 20100086522) as evidenced by Smith et al (Scientific Reports, 2016, pages 1-12).
Falb et al teach use of stem cells to deliver oncolytic vaccinia virus (¶0213 and 0216). .
Enhancement of carrier cells is described in the art. As recited in claims 2-4 and 18, Bell teaches modification of a carrier cell by improving the amplification of the virus as well as to block antiviral states (see ¶0084). Some of the blockages include inactivating the IFN antiviral response as recited in claims 21 using small molecule inhibitors and shRNA that interfere with signaling (see ¶ 0085). As evidenced by Smith et al, an shRNA against TLR7 as cited by Bell acts so that IFNa/b activity is interfered with so to prevent an antiviral state (page 1, 1st after the abstract). This will meet the limitations of claim 31 and 33.
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to incorporate the incorporate the enhancements as detailed by Bell et al in the carrier system of Falb et al. Such a modification would have resulted in a carrier of claims 1-4, 6-8, 16-18, 21, 30, 31 and 33. As noted above: 1) Falb et al teach use of stem cell carriers for oncolytic vaccinia; 2) Bell teach a number of predictable modifications for improvement of the carrier cell . Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the modified cell would allow improved treatment.
Double Patenting
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-4, 6-8, 16-18 and 30 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-63 of U.S. Patent 11,655,455.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in U.S. Patent 11,655,455. That is, the cited claims of U.S. Patent 11,655,455 anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, U.S. Patent 11,655,455 is drawn to a system comprising the cell of the instant claims that furthermore comprises vaccinia virus. The cell in both cases is modified for enhanced amplification or immunosuppressive properties. The safe harbor for non-statutory double patenting only applies for applications filed as divisional applications. Because all sets of claims are drawn to a cell carrier comprising oncolytic vaccinia and methods of use in the U.S. Patent 11,655,455, the claims are related under the non-statutory double patenting statute. The U.S. Patent 11,655,455 has not been filed as divisional applications.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the U.S. Patent 11,655,455, then two different assignees would hold a patent to the claimed invention of U.S. Patent 11,655,455, and thus improperly there would be possible harassment by multiple assignees.
Claims 1-4, 6-8, 16-18 and 30 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-42 of copending application 18/295,171.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in copending application 18/295,171. That is, the cited claims of copending application 18/295,171 anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, copending application 18/295,171 is drawn to a system comprising the cell of the instant claims that furthermore comprises vaccinia virus. The cell in both cases is modified for enhanced amplification or immunosuppressive properties. The safe harbor for non-statutory double patenting only applies for applications filed as divisional applications. Because all sets of claims are drawn to a cell carrier comprising oncolytic vaccinia and methods of use in the copending application 18/295,171, the claims are related under the non-statutory double patenting statute. The copending application 18/295,171 has not been filed as divisional applications.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the copending application 18/295,171, then two different assignees would hold a patent to the claimed invention of copending application 18/295,171, and thus improperly there would be possible harassment by multiple assignees.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-4, 6-8, 16-18 and 30 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-5, 13-16, 20, 29, 30 and 35-37 of U.S. Patent 11,505,782.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in U.S. Patent 11,505,782. That is, the cited claims of U.S. Patent 11,505,782 anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, U.S. Patent 11,505,782 is drawn to a system comprising the cell of the instant claims that furthermore comprises vaccinia virus. The cell in both cases is modified for enhanced amplification or immunosuppressive properties. The safe harbor for non-statutory double patenting only applies for applications filed as divisional applications. Because all sets of claims are drawn to a cell carrier comprising oncolytic vaccinia and methods of use in the U.S. Patent 11,505,782, the claims are related under the non-statutory double patenting statute. The U.S. Patent 11,505,782 has not been filed as divisional applications.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the U.S. Patent 11,505,782, then two different assignees would hold a patent to the claimed invention of U.S. Patent 11,505,782, and thus improperly there would be possible harassment by multiple assignees.
Conclusion
Claims 34 and 35 appears to be free of the art suppression of said receptors not found in the art to improve stem cell carriers for oncolytic virus.
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/MARIA MARVICH/ Primary Examiner, Art Unit 1634