Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 14-27 are pending and currently under examination.
Priority
This application is a continuation of application 16/807,610 filed on 03/03/2020, now U.S. Patent 11,723,937, which is a continuation of application 15/864,217 filed on 01/08/2018, now U.S. Patent 10,610,553, which is also continuation of application 15/380,728 filed 12/15/2016, now U.S. Patent 9,861,668, which is a continuation of application 14/395,388 filed 10/17/2014, now U.S. Patent 9,555,067. Applicant’s claim for the benefit of a prior-filed application provisional application 61/635,164 filed on 04/18/2012 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Claim Objections
Claims 14, 16, 21, and 23 objected to because of the following informalities:
The Examiner recommends adding “(VSV)” after the first recitation of “vesicular stomatitis viruses” in claims 14 and 21.
Additionally, the Examiner recommends reciting “sodium iodide symporter (NIS) polypeptide” in claims 16 and 23.
Appropriate correction is required.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/11/2024 is considered by the examiner.
Claim Rejections - 35 USC § 112(a)- Written Description
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.
Claims 14-27 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.
Claim 14 recites a method for treating cancer, wherein said method comprises
administering a composition comprising replication-competent vesicular stomatitis viruses to a mammal comprising cancer cells,
wherein said vesicular stomatitis viruses comprise an RNA molecule comprising
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV N polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV P polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV M polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a Paramyxovirus F polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a Paramyxovirus H polypeptide, and
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV L polypeptide,
wherein said RNA molecule lacks a nucleic acid sequence that is a template for a positive sense transcript encoding a functional VSV G polypeptide,
wherein administration of said composition to said mammal is under conditions wherein said vesicular stomatitis viruses infect said cancer cells to form infected cancer cells, and
wherein the number of cancer cells within said mammal is reduced following said administration.
Claim 21 recites a method for inducing tumor regression in a mammal, wherein said method comprises
administering a composition comprising replication-competent vesicular stomatitis viruses to a mammal comprising a tumor,
wherein said vesicular stomatitis viruses comprise an RNA molecule comprising
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV N polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV P polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV M polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a Paramyxovirus F polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a Paramyxovirus H polypeptide, and
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV L polypeptide,
wherein said RNA molecule lacks a nucleic acid sequence that is a template for a positive sense transcript encoding a functional VSV G polypeptide,
wherein administration of said composition to said mammal is under conditions wherein said vesicular stomatitis viruses infect tumor cells of said tumor to form infected tumor cells.
The Paramyxovirus H polypeptide may comprise Y481A and R533A amino acid substitutions with respect to a wild-type measles virus H polypeptide (claims 18 and 25).
The Paramyxovirus H polypeptide may comprise an amino acid sequence of a single chain antibody (claims 19 and 26) directed to EGFR, αFR, or PSMA (claims 20 and 27).
The virus may further comprise a template for a positive sense transcript encoding a NIS (claims 16 and 23). The NIS polypeptide may be a human NIS polypeptide (claims 17 and 24).
The mammal treated may be a human (claims 15 and 22).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,' to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims are broad for reciting a genus of paramyxoviruses. As written, the claims are generic to proteins found in paramyxoviruses, with only claims 18 and 25 further limiting the type of paramyxovirus to measles.
The specification offers little guidance on this genera. The specification does not disclose a list or examples of paramyxoviruses, and only refers to measles and morbillivirus (e.g., “a Paramyxovirus F polypeptide (e.g., a morbillivirus F polypeptide such as a measles virus F polypeptide)” pg. 2, lines 15-16 of specification). Additionally, measles is the only paramyxovirus in the working examples.
The art recognizes a multitude of viruses to fall under the genera of paramyxoviruses. In 2023, after the priority date of the instant application, Duprex (Duprex, W. Paul, and Rebecca Ellis Dutch. "Paramyxoviruses: pathogenesis, vaccines, antivirals, and prototypes for pandemic preparedness." The Journal of Infectious Diseases 228.Supplement_6 (2023): S390-S397.) reviewed the paramyxoviridae family, noting that it includes established human pathogens such as measles virus, mumps virus, and the human parainfluenza viruses; highly lethal zoonotic pathogens such as Nipah virus; and a number of recently identified agents, such as Sosuga virus, which remain poorly understood, and novel viruses still being identified (Abstract; pg. S392, col 2, para 2). It is known in the art that the glycoproteins of different paramyxoviruses bind to different cell surface receptors (pg. S393, col 1, para 2). These can be proteins on the plasma membrane, such as CD150 (morbillivirus receptor) and ephrin B2 (used by HeV and NiV) or moieties such as sialic acid (pg. S390, col 2, para 2). Additionally, Duprex teaches that not all paramyxoviruses are potential prototype pathogens (Figure 3). For example, Orthoviruses and pararubula viruses originate from animals, primarily bats, and were therefore considered to pose somewhat of a pandemic risk. A metaparamyxovirus has yet to be isolated and exists only as sequence information, making metaparamyxoviruses unsuitable as prototype pathogens (pg. S391, col 1, para 1). Neurotropism and endotheliotropism are observed for some, but not all, paramyxoviruses, but the molecular basis for this differential within the family has yet to be deciphered (S392, col 2, para 2).
While morbilliviruses such as measles is well-known in the art to be uniquely and highly contagious in humans, the art also recognizes substantial differences in the species of paramyxoviruses (e.g., pg. S394, “Morbilliviruses”; Figure 3-Duprex). Given the lack of knowledge in the art that the same proteins (e.g., F and H) from different species in the genera of paramyxoviruses would function the same (and what structure results in this functionality), an artisan would not assume the instant application is in possession of the claimed genera.
Furthermore, the prior art appears to be entirely silent as to making and using a hybrid VSV that comprises F and H polypeptides from any non-MV Paramyxovirus. In fact, the art recognizes that not all paramyxoviruses comprise an H protein. In 2006, Lamb (Lamb, Robert A., Reay G. Paterson, and Theodore S. Jardetzky. "Paramyxovirus membrane fusion: lessons from the F and HN atomic structures." Virology 344.1 (2006): 30-37.) taught that for many of the paramyxoviruses (NDV, PIVs 1–5 and others), the attachment protein is the hemagglutinin/neuraminidase (HN) protein, but the morbilliviruses, such as measles virus, carry a hemagglutinin (H) protein in place of HN, while the pneumoviruses (RSV) and henipaviruses (Nipah and Hendra) express a distinct attachment glycoprotein (G) (pg. 31, col 1, para 1).
The specification fails to provide evidence or guidance that a hybrid VSV that comprises F and H polypeptides from any other Paramyxovirus species would have the disclosed function of a cancer treating effect that VSV/MV(FH) hybrids have (e.g., a hybrid comprising an RSV F polypeptide, and measles H polypeptide).
In addition, claim 14 is directed to a method of treating cancer, while claim 21 is directed to a method for inducing tumor regression in a mammal. The method steps of the two claims are parallel.
Claims 21 and depending parallel Claim 14 and those depending from Claim 14. Therefore, as the claims are required to have distinct scopes, Claim 21 and depending require a generic set of tumors that are not cancerous and are required to be able to regress these tumors, without reducing the number of cancer cells as implied by Claim 14, and depending.
The specification only teaches inducing tumor regression in relation to cancer. The specification fails to provide any guidance, evidence, or suggestion of the claimed method being used to regress non-cancerous tumors, such as lipomas, hemangiomas, and neurofibromas. Additionally, the art does not mention inducing regression of lipomas, for example, using the claimed constructs.
Further, the specification fails to provide evidence of one method occurring without the other (e.g., no examples or guidance is given on how one would treat cancer using the claimed method and not also induce tumor regression, and vice versa).
Thus, in light of the implied generic nature of tumor of Claims 21 and depending, and complete lack of even contemplation of regressing non-cancerous tumors, both in the specification and art, utilizing these constructs, the Artisan would not have understood Applicant to have been in possession of the invention as claimed.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Claim Rejections - 35 USC § 112(a)- Scope of Enablement
Claims 14-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of treating cancer comprising administering a hybrid Vesicular Stomatitis Virus (VSV) that comprises F and H polypeptides from Measles Virus (MV), does not reasonably provide enablement for methods of treating cancer comprising administering a hybrid VSV that comprises F and H polypeptides from the large genus of paramyxoviruses as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Examiner incorporates herein the analysis discussed above in the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description rejection.
Claims 14 and 21 are representative of the claimed invention, and recite a method for treating cancer or inducing tumor regression in a mammal, wherein said method comprises
administering a composition comprising replication-competent vesicular stomatitis viruses to a mammal comprising cancer cells or a tumor,
wherein said vesicular stomatitis viruses comprise an RNA molecule comprising
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV N polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV P polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV M polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a Paramyxovirus F polypeptide,
a nucleic acid sequence that is a template for a positive sense transcript encoding a Paramyxovirus H polypeptide, and
a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV L polypeptide,
wherein said RNA molecule lacks a nucleic acid sequence that is a template for a positive sense transcript encoding a functional VSV G polypeptide,
wherein administration of said composition to said mammal is under conditions wherein said vesicular stomatitis viruses infect cancer or tumor cells of said tumor to form infected cancer or tumor cells.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention. If not, whether an artisan would have required undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make or use the invention based on the content of the disclosure is “undue” (In re Wands, 858 F.2d 731, 737, 8 USPQ2ds 1400, 1404 (Fed. Cir. 1988)). Furthermore, USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
The Breadth of the Claims and The Nature of the Invention
The claims are directed to a method of treating cancer and inducing tumor suppression.
The claim is broad for reasonably encompassing a large genus of paramyxoviruses.
The State of the Prior Art, The Level of One of Ordinary Skill and The Level of Predictability in the Art
The art teaches a pseudotyped VSV comprising measles F and H polypeptides. However, the art does not teach pseudotyped VSVs comprising polypeptides from other paramyxovirus species.
Shingai (Shingai, Masashi, et al. "Receptor use by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis." Journal of General Virology 84 (2003): 2133-2143.) is considered relevant prior art for teaching vesicular stomatitis virus pseudotypes expressing the envelope glycoproteins (H and F) of SSPE strains of MV. Additionally, the VSVs did not comprise G protein genes (Abstract; pg. 84-85, “Construction of pseudotype viruses and quantification in various cell types”; Figure 1).
Shingai differs from the instant application in the VSVs were not tested in vivo, only in vitro.
Tatsuo (Tatsuo, Hironobu, et al. "Virus entry is a major determinant of cell tropism of Edmonston and wild-type strains of measles virus as revealed by vesicular stomatitis virus pseudotypes bearing their envelope proteins." Journal of virology 74.9 (2000): 4139-4145.) (NPL 78 of IDS) is considered relevant prior art for teaching a recombinant vesicular stomatitis virus (VSV) containing as a reporter the green fluorescent protein gene in lieu of the VSV G protein gene (VSVdeltaG*). MV glycoproteins were efficiently incorporated into VSVdeltaG*, producing the VSV pseudotypes. VSVDG* complemented with VSV G protein efficiently infected all of the cell lines tested. The VSV pseudotype bearing the Edmonston hemagglutinin (H) and fusion (F) protein (VSVDG*-EdHF) successfully infected cell lines (Abstract).
Tatsuo differs from the instant application in the VSVs were not tested in vivo, only in vitro.
Furthermore, the prior art appears to be entirely silent as to methods of treating cancer using a hybrid VSV that comprises F and H polypeptides from any non-MV Paramyxovirus. There is no apparent evidence of record to suggest that a hybrid VSV that comprises F and H polypeptides from any other Paramyxovirus species would have the cancer treating effect that VSV/MV(FH) hybrids have.
Hastie (Hastie, Eric, and Valery Z. Grdzelishvili. "Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer." Journal of General Virology 93.12 (2012): 2529-2545.) is considered relevant art for reviewing VSV as a candidate for oncolytic virus (OV) therapy. At the time of publication (2012), few recombinant VSVs comprising foreign glycoproteins were taught in the art, with only one cited reference teaching a VSV pseudotyped with paramyxovirus F and H glycoproteins (i.e., measles) (Ayala-Brenton et al. under “Foreign glycoproteins” of Table 1; also cited below). Hastie notes that while VSV is a promising OV therapy, VSV has limitations that must be overcome for future clinical success, such as improved
oncoselectivity, safety and oncotoxicity and minimized premature immune clearance (pg. 2529, “Introduction”, para 2; pg. 2536, col 1, para 2; pg. 2540, “Concluding remarks/future directions”).
In summary, while the prior art recognizes the potential of VSVs as an oncolytic virus, the prior art is silent on hybrid VSVs comprising paramyxovirus polypeptides F and H other than those originating from measles, let alone other hybrid VSV species being used in a method of treating cancer in a mammal.
The Existence of Working Examples and The Amount of Direction Provided by the Inventor
The specification as filed does not provide any guidance or examples that would enable a skilled artisan to use the disclosed compounds or methods of using a hybrid VSV that comprises F and H polypeptides from any species of the Paramyxovirus family other than MV as claimed. Additionally, a person skilled in the art would recognize that assessing the probability of achieving a treatment effect using heretofore uncharacterized polypeptides such as those from a hybrid VSV that comprises F and H polypeptides from any non-MV species of the Paramyxovirus family is highly unpredictable.
This is particularly true in view of the lack of guidance in the specification and known unpredictability associated with the use of polypeptides that are entirely uncharacterized other than by having undefined homology to other polypeptides expressed by non-MV members of the Paramyxovirus family (e.g. other non-MV F and H polypeptides). The specification teaches that VSV could be pseudotyped to express MV-F and MV-H polypeptides, and that such hybrid viruses could be further modified to bear a single chain antibody. The hybrid virus could attach to and enter cells expressing CD46 and SLAM (i.e. MV receptors) both in vivo and in vitro. The hybrid viruses are disclosed as safe and efficacious, and capable of spreading in solid tumors. The specification presents evidence that the hybrid virus has the same tropism as MV, but looks and behaves like VSV. Evidence is also presented that the hybrid virus is perhaps more potent than unmodified MV in vitro, is not neurovirulent, and is highly active against Myeloma in mice in vivo. However, it is emphasized that no experimental data regarding VSV hybrids containing any other (i.e. non-MV) Paramyxovirus polypeptides is presented in the instant specification.
Since the quantity of experimentation required to practice the invention as claimed is undetermined, one of skill in the art would have been unable to practice the invention without engaging in undue trial and error experimentation as presented in the specification over the scope claimed.
The Quantity of Any Necessary Experimentation to Make or Use the Invention
Thus, the quantity of necessary experimentation to make or use the invention as claimed, based upon what is known in the art and what has been disclosed in the specification, will create an undue burden for a person of ordinary skill in the art to necessarily and predictably use the claimed method comprising the broadly claimed genus of hybrid VSV comprising paramyxovirus F and H polypeptides that is capable of treating cancer in a mammal.
In conclusion, the specification fails to provide any guidance as to how an artisan would have dealt with the art-recognized limitations of the claimed method commensurate with the scope of the claimed invention.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
Claims 14, 18-21, and 25-27 are rejected under pre-AIA 35 U.S.C. 102(a) as being anticipated by Ayala-Breton et al. (Ayala-Breton, Camilo, et al. "Retargeting vesicular stomatitis virus using measles virus envelope glycoproteins." Human gene therapy 23.5 (2012): 484-491.; published online December 15, 2011) (cited in Non-Final Rejection filed 05/19/2016 of Application No. 14/395,388 and the Non-Final Rejection filed 07/21/2022 for Application No. 16/807,610, of which the instant case is a continuation of). While the printed publication date of this reference occurs after the filing of the provisional application to which the instant application claims priority to, the printed publication was published online on December 15, 2011 (see final line of reference), which is prior to applicant’s earliest filing date.
Claims 14 and 21 are representative of the claimed invention, and recite a method for treating cancer or inducing tumor regression in a mammal, wherein said method comprises administering a composition comprising replication-competent vesicular stomatitis viruses to a mammal comprising cancer cells or a tumor, wherein said vesicular stomatitis viruses comprise an RNA molecule comprising a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV N polypeptide, a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV P polypeptide, a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV M polypeptide, a nucleic acid sequence that is a template for a positive sense transcript encoding a Measles F polypeptide, a nucleic acid sequence that is a template for a positive sense transcript encoding a Measles H polypeptide, and a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV L polypeptide, wherein said RNA molecule lacks a nucleic acid sequence that is a template for a positive sense transcript encoding a functional VSV G polypeptide, wherein administration of said composition to said mammal is under conditions wherein said vesicular stomatitis viruses infect cancer or tumor cells of said tumor to form infected cancer or tumor cells.
The examiner notes that while the VSVs are described as “replication-defective” in the Abstract, the VSVs are still replication-competent, as the VSVs were engineered to selectively replication in tumor cells (Discussion).
Ayala-Breton teaches a method for treating cancer or inducing tumor regression in a mammal, comprising administering a composition comprising a replication-defective vesicular stomatitis virus (VSV) to a mammal comprising cancer cells or a tumor, wherein said vesicular stomatitis viruses comprise an RNA molecule comprising a nucleic acid sequence that is a template for a positive sense transcript encoding a VSV N polypeptide, a VSV P polypeptide, a VSV M polypeptide, a Measles F polypeptide, a Measles H polypeptide, and a VSV L polypeptide, and wherein said RNA molecule lacks a nucleic acid sequence that is a template for a positive sense transcript encoding a functional VSV G polypeptide, wherein administration of said composition to said mammal is under conditions wherein said vesicular stomatitis viruses infect cancer or tumor cells of said tumor to form infected cancer or tumor cells (Abstract).
Ayala-Breton teaches a VSV deleted of its glycoprotein gene (VSVΔG), and which was pseudotyped with measles virus (MV)-F and MV-H displaying single-chain antibodies (scFv) specific for epidermal growth factor receptor (EGFR), folate receptor (FR), or prostate membrane-specific antigen (PSMA) (claims 19, 20, 26, 27) (Abstract). Ayala-Breton also teaches the use of a measles pseudotyped VSV encoding a mutated MV-H protein, with two point mutations, Y481A and R533A (claims 18 and 25). See Materials and Methods.
While Ayala-Breton does not exemplify the use of a replication-competent VSV comprising measles F and H polypeptides (VSV-FH), Ayala-Breton teaches that obtaining an oncolytic virus for human treatment requires using a replication-competent VSV-FH at page 490, left column. Ayala-Breton also does not exemplify treatment of a human. However, the tumor cells that are targeted (i.e. the xenografted tumor) are derived from a human cell line, and Ayala-Breton throughout clearly contemplates treating humans using VSV-FH, which is considered to put this embodiment in the possession of the public. The invention is thus anticipated.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 14-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Ayala-Breton (supra) as applied to claims 14, 15, 18, and 19 above, and further in view of Opyrchal et al. (Opyrchal, Mateusz, et al. "Effective radiovirotherapy for malignant gliomas by using oncolytic measles virus strains encoding the sodium iodide symporter (MV-NIS)." Human gene therapy 23.4 (2012): 419-427.) (cited in Non-Final rejection filed 05/19/2016 of Application No. 14/395, 388, of which the instant case is a continuation of).
The claimed invention is relied upon as discussed above, further comprising wherein the RNA molecule comprises a positive sense template encoding a human NIS polypeptide.
Ayala-Breton is relied upon as discussed above. The Artisan, interested in these viruses as oncolytic viruses, would be aware of Ayala-Breton, for its teaching of VSV pseudotyped with measles F and H polypeptides in order to retarget VSV to different cell receptors.
Ayala-Breton does not teach VSV-FH that comprises a positive sense template encoding a human NIS polypeptide. However, the use of the NIS polypeptide has been previously described for use in combination with an oncolytic measles virus, in order to allow for noninvasive monitoring of viral infection in vivo using iodine isotopes, as well as the augment virus-induced cytopathic effects, as taught by Opyrchal (Abstract).
The Artisan, interested in these viruses as oncolytic viruses, would be aware of Opyrchal, for its teaching of NIS polypeptide and its use in non-invasive monitoring in vitro and in vivo.
Opyrchal teaches that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor activity against glioma lines and orthotopic xenografts, which compares favorably with the MV strain expressing the human carcinoembryonic antigen, which is currently in clinical testing (at time of publishing in 2011).
It would have been obvious to one of ordinary skill in the art to engineer VSV-FH as taught by Ayala-Breton to express a human NIS polypeptide, in order to provide for noninvasive monitoring and to promote virus-induced cytopathic effects. Since the sequences of both VSV-FH as well as human NIS polypeptide were well-known in the prior art, and since both were known separately to be effective in oncolytic viral treatment methods, and because their combination would require nothing more than employing well known genetic engineering methods, one of ordinary skill in the art would have had a reasonable expectation of success in making and using the methods as claimed. Additionally, one would be motivated because as taught by Opyrchal, expression of the NIS protein, a sodium/iodine transporter, can allow noninvasive monitoring of viral infection in vitro and in vivo using iodine isotopes (pg. 419, col 2, last 3 lines). Additionally, MVs comprising NIS had significant cytopathic activity against glioblastoma cells in vitro and antitumor effect in vivo, in both settings antitumor activity was improved as compared with MV not comprising NIS (pg. 425, col 2, last para).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
Accordingly, in the absence of evidence to the contrary one of ordinary skill in the art would have considered the invention as a whole to have been prima facie obvious at the time the invention was made.
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 14-17 and 21-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9555067. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent is a species of the instant application.
Claim 14: the reference claim 1 is drawn to a method for treating cancer as presently claimed, except the paramyxovirus is further limited to being measles (i.e., a species of the paramyxoviral family).
Claim 15: the reference claim 2 further limits the mammal of the method to be human.
Claim 16: the reference claim 3 further limits the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 17: the reference claim 4 further limits the NIS polypeptide to be a human NIS polypeptide.
Claim 21: the reference claim 5 is drawn to a method for inducing tumor regression in a mammal as presently claimed, except the paramyxovirus is further limited to being measles (i.e., a species of the paramyxoviral family).
Claim 22: the reference claim 6 further limits the mammal of the method to be human.
Claim 23: the reference claim 7 further limits the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 24: the reference claim 8 further limits the NIS polypeptide to be a human NIS polypeptide.
The invention is obvious over the reference, as the reference claims a species of the claimed method. The Artisan expect success, as it is claimed subject matter.
Claims 14, 16, 18-21, 23, and 25-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 9861668. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent is a species of the instant application.
Claim 14: the reference claim 1 is drawn to a product (i.e., replication-competent vesicular stomatitis virus) used in the instantly claimed method, except the paramyxovirus is further limited to being measles (i.e., a species of the paramyxoviral family).
Claim 16: the reference claim 5 further limits the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 18: the reference claim 2 further limits the H polypeptide to be a measles virus H polypeptide comprising Y481A and R533A amino acid substitutions with respect to a wild-type measles virus H polypeptide.
Claim 19: the reference claim 3 further limits the H polypeptide comprises an amino acid sequence of a single chain antibody.
Claim 20: the reference claim 4 further limits the single chain antibody to be a single chain antibody directed to EGFR, αFR, or PSMA.
Claim 21: the reference claim 1 is drawn to a product (i.e., replication-competent vesicular stomatitis virus) used in the instantly claimed method, except the paramyxovirus is further limited to being measles (i.e., a species of the paramyxoviral family).
Claim 23: the reference claim 5 further limits the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 25: the reference claim 2 further limits the H polypeptide to be a measles virus H polypeptide comprising Y481A and R533A amino acid substitutions with respect to a wild-type measles virus H polypeptide.
Claim 26: the reference claim 3 further limits the H polypeptide comprises an amino acid sequence of a single chain antibody.
Claim 27: the reference claim 4 further limits the single chain antibody to be a single chain antibody directed to EGFR, αFR, or PSMA.
The invention is obvious over the reference, as the reference claims a species of the product used in the claimed method. The Artisan would use the product and expect success, as it is claimed subject matter.
Claims 14, 16, 17, 19-21, 23, 24, 26, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10610553. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent is a species of the instant application.
Claim 14: the reference claims 1, 5, and 9 are drawn to a product (i.e., replication-competent vesicular stomatitis virus; composition comprising the VSV; nucleic acid molecule) used in the instantly claimed method, except the paramyxovirus is further limited to being morbillivirus (i.e., a species of the paramyxoviral family).
Claim 16: the reference claim 4, 8, and 10 further limits the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 17: the reference claim 11 further limits the NIS polypeptide to be a human NIS polypeptide.
Claim 19: the reference claims 2 and 6 further limit the H polypeptide comprises an amino acid sequence of a single chain antibody.
Claim 20: the reference claims 3 and 7 further limit the single chain antibody to be a single chain antibody directed to EGFR, αFR, or PSMA.
Claim 21: the reference claims 1, 5, and 9 are drawn to a product (i.e., replication-competent vesicular stomatitis virus; composition comprising the VSV; nucleic acid molecule) used in the instantly claimed method, except the paramyxovirus is further limited to being morbillivirus (i.e., a species of the paramyxoviral family).
Claim 23: the reference claim 4, 8, and 10 further limits the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 24: the reference claim 11 further limits the NIS polypeptide to be a human NIS polypeptide.
Claim 26: the reference claims 2 and 6 further limit the H polypeptide comprises an amino acid sequence of a single chain antibody.
Claim 27: the reference claims 3 and 7 further limit the single chain antibody to be a single chain antibody directed to EGFR, αFR, or PSMA.
The invention is obvious over the reference, as the reference claims a species of the product used in the claimed method. The Artisan would use the product and expect success, as it is claimed subject matter.
Claims 14, 16-21, and 23-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11723937. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent is a species of the instant application.
Claim 14: the reference claims 1, 6, and 11 are drawn to a product (i.e., replication-competent vesicular stomatitis virus; composition comprising the VSV; nucleic acid molecule) used in the instantly claimed method.
Claim 16: the reference claims 5, 10, and 12 further limit the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 17: the reference claim 13 further limits the NIS polypeptide to be a human NIS polypeptide.
Claim 18: the reference claims 2 and 7 further limit the H polypeptide to be a measles virus H polypeptide comprising Y481A and R533A amino acid substitutions with respect to a wild-type measles virus H polypeptide.
Claim 19: the reference claims 3 and 8 further limit the H polypeptide to comprise an amino acid sequence of a single chain antibody.
Claim 20: the reference claims 4 and 9 further limit the single chain antibody to be a single chain antibody directed to EGFR, αFR, or PSMA.
Claim 21: the reference claims 1, 6, and 11 are drawn to a product (i.e., replication-competent vesicular stomatitis virus; composition comprising the VSV; nucleic acid molecule) used in the instantly claimed method.
Claim 23: the reference claims 5, 10, and 12 further limit the RNA molecule to comprise a nucleic acid sequence that is a template for a positive sense transcript encoding a NIS polypeptide.
Claim 24: the reference claim 12 further limits the NIS polypeptide to be a human NIS polypeptide.
Claim 25: the reference claims 2 and 7 further limit the H polypeptide to be a measles virus H polypeptide comprising Y481A and R533A amino acid substitutions with respect to a wild-type measles virus H polypeptide.
Claim 26: the reference claims 3 and 8 further limit the H polypeptide to comprise an amino acid sequence of a single chain antibody.
Claim 27: the reference claims 4 and 9 further limit the single chain antibody to be a single chain antibody directed to EGFR, αFR, or PSMA.
The invention is obvious over the reference, as the reference claims the product used in the claimed method. The Artisan would use the product and expect success, as it is claimed subject matter.
Conclusion
No claims are allowed.
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ALLISON M. JOHNSON
Examiner
Art Unit 1638
/ALLISON MARIE JOHNSON/ Examiner, Art Unit 1638
/ROBERT M KELLY/ Primary Examiner, Art Unit 1638